Measurement of Smooth Muscle Function in the Isolated Tissue Bath-applications to Pharmacology Research

Isolated tissue bath assays are a classical pharmacological tool for evaluating concentration-response relationships in a myriad of contractile tissues.  ...

University of Vermont College of Medicine

Endothelin receptors (ET(A) and ET(B)) mediate responses to ET-1. ET(B) receptor function seems to differ between a similarly sized arterial and venous pair, the rat vena cava (RVC) and rat thoracic aorta (RA). ET(B) receptors mediate RVC contraction directly, but it is unclear whether ET(B) receptors mediate contraction in RA. Because of these apparent differences in ET(B) receptor-mediated vascular contraction, we hypothesize that relaxant ET(B)-receptor mechanisms in RVC would be different from those in RA. RA and RVC rings were isolated from rats for measurement of isometric contraction. When contracted with prostaglandin F-2alpha (PGF-2alpha) (20 microM), the ET(B) receptor agonist sarafotoxin-6c (S6c) (100 nM) significantly relaxed RA and RVC. N(omega)-Nitro-L-arginine (LNNA) (100 microM) or endothelial denudation abolished relaxation to S6c in RA. By contrast, S6c-induced relaxation of RVC was attenuated but not abolished by LNNA and endothelial denudation. RVC (PGF-2alpha-contracted) relaxed to low concentrations of ET-1, whereas under the same conditions RA responded with contraction. ET-1-induced relaxation in RA was observed only with ET(A) receptor blockade. Vessels from dopamine-beta-hydroxylase-ET(B) transgenic rats, which lack functional ET(B) receptors in the vasculature, were also used. RVC (PGF-2alpha-contracted) from these rats did not relax to ET-1. Thus, although both RA and RVC possess endothelial relaxant ET(B) receptors, RA and RVC differ in that relaxant ET(B) receptors may also be present in smooth muscle of RVC. Moreover, the mechanisms of endothelial cell ET(B) receptor-mediated relaxation in RA and RVC are not the same.

Endothelin ET(B) receptors in arteries and veins: multiple actions in the vein.

The 21-amino-acid peptide ET-1 (endothelin-1) regulates a diverse array of physiological processes, including vasoconstriction, angiogenesis, nociception and cell proliferation. Most of the effects of ET-1 are associated with an increase in intracellular calcium concentration. The calcium influx and mobilization pathways activated by ET-1, however, vary immensely. The present review begins with the basics of calcium signalling and investigates the different ways intracellular calcium concentration can increase in response to a stimulus. The focus then shifts to ET-1, and discusses how ET receptors mobilize calcium. We also examine how disease alters calcium-dependent responses to ET-1 by discussing changes to ET-1-mediated calcium signalling in hypertension, as there is significant interest in the role of ET-1 in this important disease. A list of unanswered questions regarding ET-mediated calcium signals are also presented, as well as perspectives for future research of calcium mobilization by ET-1.

The interdependence of endothelin-1 and calcium: a review.

The Na(+)/Ca(2+) exchanger (NCX) is a bi-directional regulator of cytosolic Ca(2+), causing Ca(2+) efflux in forward-mode and Ca(2+) influx in reverse-mode. We hypothesized that reverse-mode NCX is a means of Ca(2+) entry in rat aorta (RA) and vena cava (RVC). NCX protein in RA and RVC was confirmed by immunoprecipitation. To assess NCX function, isometric contraction and intracellular Ca(2+) was measured in RA and RVC rings in response to low extracellular Na(+), endothelin-1 (ET-1), and KCl, in the presence or absence of the NCX antagonist KB-R7943. In RVC, low extracellular Na(+) caused vasoconstriction and an increase in intracellular Ca(2+) that was attenuated by 10μM KB-R7943. KB-R7943 (10 μM) attenuated maximal contraction to ET-1 in RVC (53 ± 9% of control), but not RA (91±1% of control). KB-R7943 (10 μM) reduced the maximal contraction to KCl in RA (48 ± 5%) and nearly abolished it in RVC (9 ± 2%), suggesting that voltage-dependent Ca(2+) influx may be inhibited by KB-R7943 as well. However, the L-type Ca(2+) channel inhibitor nifedipine (1 μM) did not alter ET-1-induced contraction. Our findings suggest that reverse-mode NCX is an important mechanism of Ca(2+) influx in RVC but not RA, especially during ET-1-induced contraction. Also, the effects of KB-R7943 on ET-1-induced contraction of RA and RVC are predominantly mediated by reverse-mode NCX inhibition and not due to off-target inhibition of Ca(2+) channels.

Reverse-mode Na+/Ca2+ exchange is an important mediator of venous contraction.

5-&#x7F9F;&#x8272;&#x80FA; (5-&#x7F9F;&#x8272;&#x80FA;&#xFF0C;5-&#x7F9F;&#x8272;&#x80FA;) 7 &#x5929;&#x8F93;&#x6DB2;&#x5BFC;&#x81F4;&#x6301;&#x7EED;&#x7684;&#x4E0B;&#x964D;&#x4E2D;&#x63D0;&#x5347;&#x8840;&#x538B;&#x7684;&#x7537;&#x6027;&#x53BB;&#x6C27;&#x76AE;&#x8D28;&#x916E; (DOCA) &#x918B;&#x9178;&#x916F;-&#x76D0;&#x9F20;&#x3002;&#x9AD8;&#x8840;&#x538B;&#x662F;&#x4E00;&#x79CD;&#x957F;&#x671F;&#x7684;&#x75BE;&#x75C5;&#xFF0C;&#x6211;&#x4EEC;&#x76EE;&#x524D;&#x6D4B;&#x8BD5;&#x8FD9;&#x4E2A;&#x5047;&#x8BBE;&#xFF0C;&#x8F83;&#x957F;&#x7684; &#xFF08;30 &#x5929;&#xFF09; 5-&#x7F9F;&#x8272;&#x80FA;&#x8F93;&#x6DB2;&#x53EF;&#x80FD;&#x5BFC;&#x81F4; DOCA-&#x76D0;&#x65E2;&#x5B9A;&#x7684;&#x9AD8;&#x8840;&#x538B;&#x5927;&#x9F20;&#x8840;&#x538B;&#x6301;&#x7EED;&#x7684;&#x4E0B;&#x964D;&#x3002;&#x6B64;&#x65F6;&#x95F4;&#x6BB5;&#x5185; &#xFF08;&sim;4 &#x5468;&#xFF09; &#x4E5F;&#x4E0D;&#x8DB3;&#x4EE5;&#x6D4B;&#x8BD5;&#x662F;&#x5426; 5-&#x7F9F;&#x8272;&#x80FA;&#x80FD;&#x51CF;&#x8F7B; DOCA-&#x76D0;&#x9AD8;&#x8840;&#x538B;&#x7684;&#x53D1;&#x5C55;&#x3002;5-&#x7F9F;&#x8272;&#x80FA; (25 &#x6700;&#x5C0F;&#x5FAE;&#x514B;/&#x5343;&#x514B; &#xFF1B; sc) &#x6216;&#x8F66;&#x8F86; (Veh) &#x5DF2;&#x9001;&#x4EA4;&#x901A;&#x8FC7;&#x6E17;&#x900F;&#x6CF5; (1) &#x5EFA;&#x7ACB; DOCA-&#x76D0;&#x5927;&#x9F20; 1 &#x4E2A;&#x6708;&#xFF0C;(2) &#x5927;&#x9F20;&#x524D;&#x4E00;&#x4E2A;&#x6708;&#x548C;&#x8840;&#x538B;&#x548C;&#x5FC3;&#x7387;&#x6D4B;&#x91CF; telemetrically-DOCA-&#x76D0;&#x7BA1;&#x7406;&#x3002;5-&#x7F9F;&#x8272;&#x80FA;&#x8F93;&#x6DB2;&#x7684;&#x6700;&#x540E;&#x4E00;&#x5929;&#xFF0C;&#x514D;&#x8D39;&#x8840;&#x5C0F;&#x677F;&#x8840;&#x6D46; 5-&#x7F9F;&#x8272;&#x80FA;&#x6D53;&#x5EA6;&#x90FD;&#x660E;&#x663E;&#x9AD8;&#x4E8E;&#x7B2C; 5-&#x7F9F;&#x8272;&#x80FA;&#x4E0E; Veh &#x6CE8;&#x5165;&#x5927;&#x9F20;&#xFF0C;&#x548C;&#x5E73;&#x5747;&#x52A8;&#x8109;&#x538B;&#x4E2D; 5-&#x7F9F;&#x8272;&#x80FA;&#x6CE8;&#x5165; (135 &plusmn; 4 &#x6BEB;&#x7C73;&#x6C5E;&#x67F1; vs Veh &#x6CE8;&#x5165; 151 &#x6BEB;&#x7C73; &plusmn; 7 &#x6C5E;&#x67F1;) &#x662F;&#x4F4E;&#x5F97;&#x53EF;&#x601C;&#x5EFA;&#x7ACB;&#x5927;&#x9F20; DOCA-&#x76D0;&#x3002;&#x76F8;&#x6BD4;&#x4E4B;&#x4E0B;&#xFF0C;5-&#x7F9F;&#x8272;&#x80FA;-&#x8F93;&#x6DB2;&#x5E76;&#x4E0D;&#x59A8;&#x788D;&#x53D1;&#x5C55;&#x7684; DOCA-&#x76D0;&#x9AD8;&#x8840;&#x538B; (144 &plusmn; 7 &#x6BEB;&#x7C73;&#x6C5E;&#x67F1; vs Veh = 156 &plusmn; 6 &#x6BEB;&#x7C73;&#x6C5E;&#x67F1;)&#x3002;&#x80F8;&#x4E3B;&#x52A8;&#x8109;&#x6761;&#x7684;&#x7B49;&#x957F;&#x6536;&#x7F29;&#x8861;&#x91CF;&#xFF0C;&#x548C;&#x6548;&#x529B;&#x548C;&#x6700;&#x5927;&#x503C;&#x90FD;&#x4E0D;&#x6536;&#x7F29;&#x5230;&#x963F;&#x5C14;&#x6CD5;&#x80BE;&#x4E0A;&#x817A;&#x7D20;&#x80FD;&#x53D7;&#x4F53;&#x6FC0;&#x52A8;&#x5242;&#x82EF;&#x80BE;&#x4E0A;&#x817A;&#x7D20; (PE) &#x6216; 5-&#x7F9F;&#x8272;&#x80FA;&#x5DF2;&#x88AB;&#x4FEE;&#x6539;&#x8F93;&#x6CE8;&#x5BF9; 5-&#x7F9F;&#x8272;&#x80FA; &#xFF08;&#x65E2;&#x5B9A;&#x6216;&#x9884;&#x9632;&#x6027;&#x8F93;&#x6DB2;)&#xFF0C;&#x5E76;&#x6700;&#x5927;&#x4E3B;&#x52A8;&#x8109;&#x653E;&#x5BBD;&#x5BF9;&#x4E59;&#x9170;&#x80C6;&#x78B1; &#xFF08;ACh&#xFF09; &#x662F;&#x6E29;&#x548C;&#x4F46;&#x4E0D;&#x662F;&#x663E;&#x8457;&#x589E;&#x5F3A; (&sim;15%&#x6539;&#x8FDB;)&#x3002;&#x8FD9;&#x9879;&#x7814;&#x7A76;&#x8868;&#x660E; 5-&#x7F9F;&#x8272;&#x80FA;&#x662F;&#x80FD;&#x591F;&#x964D;&#x4F4E;&#x65E2;&#x5B9A; DOCA-&#x76D0;&#x9AD8;&#x8840;&#x538B;&#x5927;&#x9F20;&#x8840;&#x538B;&#x7684;&#x8FC7;&#x53BB;&#x7684;&#x4E00;&#x4E2A;&#x6708;&#x4E2D;&#xFF0C;&#x4E0D;&#x4F1A;&#x5927;&#x5E45;&#x5EA6;&#x4FEE;&#x6539;&#x6216;&#x4F9D;&#x8D56;&#x4E8E;&#x5DF2;&#x4FEE;&#x6539;&#x7684;&#x8840;&#x7BA1;&#x53CD;&#x5E94;&#x6027;&#x7684;&#x673A;&#x5236;&#x3002;&#x8FD9;&#x4E00;&#x53D1;&#x73B0;&#x5C06;&#x6253;&#x5F00; 5-&#x7F9F;&#x8272;&#x80FA;&#x6C34;&#x5E73;&#x7684;&#x63D0;&#x5347;&#x53EF;&#x80FD;&#x662F;&#x6709;&#x7528;&#x7684;&#x5728;&#x6CBB;&#x7597;&#x9AD8;&#x8840;&#x538B;&#x75C5;&#x7684;&#x53EF;&#x80FD;&#x6027;&#x3002;

&#x5728;&#x957F;&#x65F6;&#x95F4;&#x4E3A;&#x671F;&#x4E00;&#x4E2A;&#x6708;&#x7684; 5-&#x7F9F;&#x8272;&#x80FA;&#x8F93;&#x6DB2;&#x7ED3;&#x679C;&#x53BB;&#x6C27;&#x76AE;&#x8D28;&#x916E; (DOCA) &#x918B;&#x9178;&#x76D0;&#x9AD8;&#x8840;&#x538B;&#x5927;&#x9F20;&#x7684;&#x8840;&#x538B;&#x4E0B;&#x964D;&#x3002;

A 7-day infusion of serotonin (5-hydroxytryptamine, 5-HT) causes a sustained fall in elevated blood pressure in the male deoxycorticosterone acetate (DOCA)-salt rat. As hypertension is a long-term disease, we presently test the hypothesis that a longer (30 day) 5-HT infusion could cause a sustained fall in blood pressure in the established hypertensive DOCA-salt rat. This time period (âˆ¼4 weeks) was also sufficient to test whether 5-HT could attenuate the development of DOCA-salt hypertension. 5-HT (25 Î¼g/kg/min; sc) or vehicle (Veh) was delivered via osmotic pump to (1) established DOCA-salt rats for one month, (2) Sprague-Dawley rats prior to DOCA-salt administration for one month, and blood pressure and heart rate measured telemetrically. On the final day of 5-HT infusion, free platelet poor plasma 5-HT concentrations were significantly higher in 5-HT versus Veh-infused rats, and mean arterial pressure was significantly lower in 5-HT-infused (135 Â± 4 mmHg vs Veh-infused 151 Â± 7 mmHg) established DOCA-salt rats. By contrast, 5-HT-infusion did not prevent the development of DOCA-salt hypertension (144 Â± 7 mmHg vs Veh = 156 Â± 6 mmHg). Isometric contraction of aortic strips was measured, and neither the potency nor maximum contraction to the alpha adrenergic receptor agonist phenylephrine (PE) or 5-HT were modified by infusion of 5-HT (established or preventative infusion), and maximum aortic relaxation to acetylcholine (ACh) was modestly but not significantly enhanced (âˆ¼15% improvement). This study demonstrates 5-HT is capable of lowering blood pressure in established DOCA-salt hypertensive rats over the course of one month in a mechanism that does not significantly modify or is dependent on modified vascular responsiveness. This finding opens the possibility that elevation of 5-HT levels could be useful in the treatment of hypertension.

One-Month Serotonin Infusion Results in a Prolonged Fall in Blood Pressure in the Deoxycorticosterone Acetate (DOCA) Salt Hypertensive Rat.

Une infusion de 7 jours de la s&eacute;rotonine (5-hydroxytryptamine, 5-HT) provoque une baisse soutenue de la tension art&eacute;rielle &eacute;lev&eacute;e dans l&#39;ac&eacute;tate de d&eacute;soxycorticost&eacute;rone m&acirc;le (DOCA)-rat de sel. Que l&#39;hypertension est une maladie &agrave; long terme, nous testons actuellement l&#39;hypoth&egrave;se selon laquelle une perfusion de 5-HT (30 jours) plus longue pourrait provoquer une baisse soutenue dans la pression art&eacute;rielle chez le rat hypertensif &eacute;tablis DOCA-sel. Ce laps de temps (semaines &sim;4) &eacute;tait &eacute;galement suffisant pour tester si la 5-HT pourrait att&eacute;nuer le d&eacute;veloppement de l&#39;hypertension DOCA-sel. 5-HT (25 &mu;g/kg/min; sc) ou un v&eacute;hicule (Veh) fournie via une pompe osmotique &agrave; des rats DOCA-sel (1) &eacute;tablies pendant un mois, (2) rats Sprague-Dawley avant l&#39;administration de DOCA-sel pour un mois et la tension art&eacute;rielle et fr&eacute;quence cardiaque mesur&eacute;e telemetrically. Le dernier jour de la perfusion de 5-HT, libre plaquettaire faible concentrations plasmatiques de la 5-HT &eacute;taient significativement plus &eacute;lev&eacute;es dans la 5-HT que chez les rats v&eacute;h infus&eacute;, et la pression art&eacute;rielle moyenne &eacute;tait significativement plus faible en moyenne 5-HT-infus&eacute; (135 &plusmn; 4 vs infus&eacute; v&eacute;h 151 &plusmn; 7 mmHg) &eacute;tabli chez les rats DOCA-sel. En revanche, la 5-HT-perfusion n&#39;a pas emp&ecirc;ch&eacute; le d&eacute;veloppement de l&#39;hypertension DOCA-sel (144 &plusmn; 7 mmHg vs v&eacute;h = 156 &plusmn; 6 mmHg). Contraction isom&eacute;trique des bandes aortiques a &eacute;t&eacute; mesur&eacute;e, ni la puissance ni le maximum la contraction induite par les r&eacute;cepteurs adr&eacute;nergiques alpha agoniste ph&eacute;nyl&eacute;phrine (PE) ou 5-HT ont &eacute;t&eacute; modifi&eacute;s par une perfusion de 5-HT (perfusion &eacute;tablie ou pr&eacute;ventive) et une d&eacute;tente maximum aortique &agrave; l&#39;ac&eacute;tylcholine (ACh) a &eacute;t&eacute; modestement mais pas significativement am&eacute;lior&eacute;e (&sim;15 % d&#39;am&eacute;lioration). Cette &eacute;tude d&eacute;montre la 5-HT est capable de faire baisser la pression art&eacute;rielle chez les rats hypertendus DOCA-sel &eacute;tablis au cours d&#39;un mois dans un m&eacute;canisme qui ne modifie pas significativement ou d&eacute;pend de la r&eacute;activit&eacute; vasculaire mis &agrave; jour le. Cette d&eacute;couverte ouvre la possibilit&eacute; que l&#39;&eacute;l&eacute;vation des niveaux de 5-HT pourrait &ecirc;tre utile dans le traitement de l&#39;hypertension.

R&eacute;sultats de perfusion de s&eacute;rotonine un mois dans une longue chute art&eacute;rielle chez le Rat hypertendu sel de d&eacute;soxycorticost&eacute;rone ac&eacute;tate (DOCA).

Eine 7-Tage-Infusion von Serotonin (5-Hydroxytryptamin, 5-HT) verursacht einen anhaltenden R&uuml;ckgang in erh&ouml;hter Blutdruck in den m&auml;nnlichen Deoxycorticosterone-Acetat (DOCA)-Salz Ratte. Bluthochdruck ist eine langfristige Krankheit, testen wir derzeit die Hypothese, die eine l&auml;ngere (30 Tage) 5-HT-Infusion einen anhaltenden R&uuml;ckgang des Blutdrucks in der etablierten Hypertensive DOCA-Salz-Ratte verursachen k&ouml;nnten. Dieses Zeitraums (&sim;4 Wochen) reichte auch testen, ob 5-HT die Entwicklung von DOCA-Salz Bluthochdruck d&auml;mpfen k&ouml;nnte. 5-HT (25 &mu;g/kg/min; sc) oder Fahrzeug (Veh) wurde &uuml;ber osmotischen Pumpe (1) etablierten DOCA-Salz-Ratten einen Monat lang (2) Sprague-Dawley Ratten vor DOCA-Salz-Administration f&uuml;r einen Monat, und Blutdruck und Herzfrequenz telemetrisch gemessene geliefert. Am letzten Tag der 5-HT-Infusion gegr&uuml;ndet Armen 5-HT-Plasmakonzentrationen waren signifikant h&ouml;her in 5-HT gegen Veh-Infusion Ratten und mittleren arteriellen Druck war deutlich niedriger in 5-HT-Infusion (135 &plusmn; 4 MmHg vs. Veh-Infusion 151 &plusmn; 7 MmHg) Kostenlose Thrombozyten DOCA-Salz-Ratten. Im Gegensatz dazu 5-HT-Infusion nicht verhindern die Entwicklung von DOCA-Salz Bluthochdruck (144 &plusmn; 7 MmHg vs. Veh = 156 &plusmn; 6 MmHg). Isometrische Kontraktion der Aorten-Streifen wurde gemessen, und weder die Wirksamkeit noch die maximale Kontraktion der alpha adrenerge Rezeptor-Agonist Phenylephrin (PE) oder 5-HT durch Infusion von 5-HT (etablierte oder vorbeugende Infusion) ver&auml;ndert wurden und maximale Aorten Entspannung an Acetylcholin (ACh) war bescheiden, aber nicht erheblich verbessert (&sim;15 % Verbesserung). Diese Studie zeigt, dass die 5-HT ist Lage, Senkung des Blutdrucks bei etablierten DOCA-Salz Hypertensive Ratten im Laufe eines Monats in einen Mechanismus, der nicht wesentlich &auml;ndern oder ge&auml;nderte vaskul&auml;re Reaktionsf&auml;higkeit abh&auml;ngig ist. Diese Erkenntnis er&ouml;ffnet die M&ouml;glichkeit, dass die Erh&ouml;hung von 5-HT-Ebenen in der Behandlung von Bluthochdruck n&uuml;tzlich sein k&ouml;nnte.

Einmonatige Serotonin Infusion f&uuml;hrt zu einer l&auml;ngeren fallen des Blutdrucks in der Deoxycorticosterone-Acetat (DOCA) Salz Hypertensive Ratte.

Un infuso di 7 giorni di serotonina (5-idrossitriptamina, 5-HT) provoca una caduta sostenuta nella pressione sanguigna elevata in acetato (DOCA) maschio deoxycorticosterone-ratto salata. Come l&#39;ipertensione &egrave; una malattia a lungo termine, attualmente il test l&#39;ipotesi che un infusione di 5-HT (30 giorni) pi&ugrave; lungo potrebbe causare una sostenuta caduta della pressione sanguigna in ratti ipertesi stabilito DOCA-sale. Questo periodo di tempo (settimane &sim;4) &egrave; stato sufficiente per verificare se la 5-HT potrebbe attenuare lo sviluppo di ipertensione DOCA-sale. 5-HT (25 &mu;g/kg/min; sc) o veicolo (Veh) &egrave; stato recapitato tramite pompa osmotica ratti DOCA-sale (1) stabiliti per un mese, ratti Sprague-Dawley (2) prima della somministrazione di DOCA-sale per un mese e la pressione sanguigna e frequenza cardiaca misurata telemetrically. L&#39;ultimo giorno di infusione di 5-HT, libero piastrinica scarsa concentrazioni di 5-HT sono stati significativamente pi&ugrave; alta di 5-HT contro ratti Veh-infuso, e pressione arteriosa media &egrave; stata significativamente inferiore a 5-HT-infuso (135 &plusmn; 4 mmHg vs Veh-infuso 151 &plusmn; 7 mmHg) stabilito ratti DOCA-sale. Al contrario, 5-HT-infusione non ha impedito lo sviluppo di ipertensione DOCA-sale (144 &plusmn; 7 mmHg vs Veh = 156 &plusmn; 6 mmHg). Contrazione isometrica delle strisce aortiche &egrave; stata misurata e n&eacute; la potenza n&eacute; la massima contrazione per la Fenilefrina di agonista del recettore adrenergico alfa (PE) o 5-HT sono stati modificati dall&#39;infusione di 5-HT (infusione stabilita o preventiva), e massimo relax aortico di acetilcolina (ACh) era modestamente ma non significativamente migliorata (&sim;15% di miglioramento). Questo studio dimostra la 5-HT &egrave; in grado di abbassamento della pressione arteriosa in stabilito ratti ipertesi DOCA-sale nel corso di un mese in un meccanismo che non modifica in modo significativo o &egrave; dipendente da modificata reattivit&agrave; vascolare. Questa scoperta apre la possibilit&agrave; che l&#39;elevazione dei livelli di 5-HT potrebbe essere utile nel trattamento dell&#39;ipertensione.

Risultati infusione della serotonina un mese in una prolungata cadono della pressione sanguigna in ratti ipertesi sale Deoxycorticosterone acetato (DOCA).

&#x30BB;&#x30ED;&#x30C8;&#x30CB;&#x30F3; (5-ht&#x3001;5 HT&#xFF09; &#x306E; 7 &#x65E5;&#x9593;&#x6CE8;&#x5165;&#x306B;&#x3088;&#x308A;&#x6301;&#x7D9A;&#x7684;&#x306A;&#x8840;&#x5727;&#x306E;&#x4E0A;&#x6607; &#xFF08;DOCA&#xFF09; &#x7537;&#x6027; doca-&#x5869;&#x306E;&#x30E9;&#x30C3;&#x30C8;&#x3002;&#x9AD8;&#x8840;&#x5727;&#x306F;&#x9577;&#x671F;&#x7684;&#x306A;&#x75C5;&#x6C17;&#x3067;&#x3042;&#x308B;&#x3088;&#x3046;&#x306B;&#x3001;&#x6211;&#x3005; &#x306F;&#x73FE;&#x5728;&#x3082;&#x3046; &#xFF08;30 &#x65E5;&#xFF09; 5 HT &#x6CE8;&#x5165;&#x306E;&#x6301;&#x7D9A;&#x7684;&#x306A;&#x78BA;&#x7ACB;&#x3055;&#x308C;&#x305F; DOCA-&#x5869;&#x9AD8;&#x8840;&#x5727;&#x81EA;&#x7136;&#x767A;&#x75C7;&#x30E9;&#x30C3;&#x30C8;&#x306E;&#x8840;&#x5727;&#x3092;&#x5F15;&#x304D;&#x8D77;&#x3053;&#x3059;&#x3053;&#x3068;&#x304C;&#x4EEE;&#x8AAC;&#x3092;&#x30C6;&#x30B9;&#x30C8;&#x3057;&#x307E;&#x3059;&#x3002;&#x3053;&#x306E;&#x671F;&#x9593; (&sim;4 &#x9031;) &#x3082; 5 HT DOCA-&#x5869;&#x9AD8;&#x8840;&#x5727;&#x767A;&#x75C7;&#x3092;&#x6E1B;&#x8870;&#x3055;&#x305B;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x308B;&#x304B;&#x3069;&#x3046;&#x304B;&#x3092;&#x30C6;&#x30B9;&#x30C8;&#x3059;&#x308B;&#x306E;&#x306B;&#x5341;&#x5206;&#x3060;&#x3063;&#x305F;&#x3002;5 HT &#xFF08;sc 25 &mu; g/kg/&#x5206;&#xFF09; &#x307E;&#x305F;&#x306F;&#x8ECA; &#xFF08;&#x8ECA;&#x4E21;&#xFF09; &#x3092;&#x4ECB;&#x3057;&#x3066;&#x6D78;&#x900F;&#x5727;&#x30DD;&#x30F3;&#x30D7; (1) &#x8A2D;&#x7ACB; DOCA-&#x5869;&#x306E;&#x30E9;&#x30C3;&#x30C8;&#x306B; 1 &#x30F6;&#x6708; &#xFF08;2&#xFF09; Sd &#x30E9;&#x30C3;&#x30C8; DOCA-&#x5869;&#x6295;&#x4E0E; 1 &#x30F6;&#x6708;&#x3001;&#x8840;&#x5727;&#x3068;&#x5FC3;&#x62CD;&#x6570; telemetrically &#x6E2C;&#x5B9A;&#x306E;&#x524D;&#x306B;&#x914D;&#x4FE1;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;5 HT &#x6CE8;&#x5165;&#x306E;&#x6700;&#x7D42;&#x65E5;&#x306B;&#x306F;&#x3001;&#x7121;&#x6599;&#x8840;&#x5C0F;&#x677F;&#x8840;&#x6F3F;&#x30BB;&#x30ED;&#x30C8;&#x30CB;&#x30F3; 5-HT Veh &#x6CE8;&#x5165;&#x30E9;&#x30C3;&#x30C8;&#x5BFE;&#x3067;&#x6709;&#x610F;&#x306B;&#x9AD8;&#x304B;&#x3063;&#x305F;&#x3057;&#x3001;&#x5E73;&#x5747;&#x52D5;&#x8108;&#x5727; 5 HT &#x6CE8;&#x5165; (135 &plusmn; 4 mmHg &#x5BFE; Veh &#x6CE8;&#x5165; 151 &plusmn; 7 mmHg &#x3067;&#x6709;&#x610F;&#x306B;&#x4F4E;&#x304B;&#x3063;&#x305F;&#x8CA7;&#x3057;&#x3044; DOCA-&#x5869;&#x30E9;&#x30C3;&#x30C8;&#x3092;&#x8A2D;&#x7ACB;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x5BFE;&#x7167;&#x7684;&#x306B;&#x3001;5 HT &#x6CE8;&#x5165; DOCA-&#x5869;&#x9AD8;&#x8840;&#x5727;&#x767A;&#x75C7;&#x3092;&#x4E88;&#x9632;&#x3057;&#x306A;&#x304B;&#x3063;&#x305F; (144 &plusmn; 7 mmHg &#x5BFE; Veh = 156 &plusmn; 6 mmHg)&#x3002;&#x5927;&#x52D5;&#x8108;&#x306E;&#x30B9;&#x30C8;&#x30EA;&#x30C3;&#x30D7;&#x306E;&#x7B49;&#x5C3A;&#x6027;&#x53CE;&#x7E2E;&#x3092;&#x6E2C;&#x5B9A;&#x3057;&#x529B;&#x3082;&#x6700;&#x5927;&#x306E;&#x53CE;&#x7E2E;&#x3092; &alpha; &#x30A2;&#x30C9;&#x30EC;&#x30CA;&#x30EA;&#x30F3;&#x53D7;&#x5BB9;&#x4F53;&#x30A2;&#x30B4;&#x30CB;&#x30B9;&#x30C8; &#x30D5;&#x30A7;&#x30CB;&#x30EC;&#x30D5;&#x30EA;&#x30F3; (PE) &#x307E;&#x305F;&#x306F; 5 HT 5 HT &#xFF08;&#x6CE8;&#x5165;&#xFF09; &#x8A2D;&#x7ACB;&#x3084;&#x4E88;&#x9632;&#x306E;&#x6CE8;&#x5165;&#x306B;&#x3088;&#x3063;&#x3066;&#x5909;&#x66F4;&#x3055;&#x308C;&#x3001;&#x30A2;&#x30BB;&#x30C1;&#x30EB;&#x30B3;&#x30EA;&#x30F3; (ACh) &#x3078;&#x306E;&#x6700;&#x5927;&#x306E;&#x5927;&#x52D5;&#x8108;&#x7DE9;&#x548C;&#x3055;&#x308C;&#x305F;&#x63A7;&#x3048;&#x3081;&#x3067;&#x306F;&#x306A;&#x304F; &#xFF08;&sim;15% &#x6539;&#x5584;&#xFF09; &#x304C;&#x5927;&#x5E45;&#x306B;&#x5411;&#x4E0A;&#x3057;&#x307E;&#x3059;&#x3002;&#x672C;&#x7814;&#x7A76;&#x3067;&#x306F;&#x3001;5 HT &#x306F; 1 &#x30F6;&#x6708;&#x3067;&#x5927;&#x5E45;&#x306B;&#x5909;&#x66F4;&#x3055;&#x308C;&#x306A;&#x3044;&#x3001;&#x307E;&#x305F;&#x306F;&#x5909;&#x66F4;&#x306E;&#x8840;&#x7BA1;&#x53CD;&#x5FDC;&#x6027;&#x306B;&#x4F9D;&#x5B58;&#x3057;&#x3066;&#x3044;&#x308B;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x306E;&#x78BA;&#x7ACB;&#x3055;&#x308C;&#x305F; DOCA-&#x5869;&#x9AD8;&#x8840;&#x5727;&#x30E9;&#x30C3;&#x30C8;&#x306E;&#x8840;&#x5727;&#x3092;&#x4E0B;&#x3052;&#x308B;&#x304C;&#x53EF;&#x80FD;&#x3067;&#x3059;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3053;&#x306E;&#x767A;&#x898B; 5 HT &#x5024;&#x306E;&#x4E0A;&#x6607;&#x304C;&#x9AD8;&#x8840;&#x5727;&#x306E;&#x6CBB;&#x7642;&#x306B;&#x6709;&#x76CA;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x53EF;&#x80FD;&#x6027;&#x3092;&#x958B;&#x304D;&#x307E;&#x3059;&#x3002;

1 &#x30F6;&#x6708;&#x30BB;&#x30ED;&#x30C8;&#x30CB;&#x30F3;&#x6CE8;&#x5165;&#x306E;&#x7D50;&#x679C;&#x9577;&#x671F;&#x306B;&#x6295;&#x4E0E;&#x3057;, &#x305D;&#x306E;&#x9162;&#x9178; &#xFF08;DOCA&#xFF09; &#x5869;&#x9AD8;&#x8840;&#x5727;&#x30E9;&#x30C3;&#x30C8;&#x306E;&#x8840;&#x5727;&#x306B;&#x843D;&#x3061;&#x308B;&#x3002;

&#xC138;&#xB85C;&#xD1A0;&#xB2CC; (5-hydroxytryptamine, 5-HT)&#xC758; 7 &#xC77C; &#xC8FC;&#xC785; &#xD558;&#xBA74; &#xB0A8;&#xC131; deoxycorticosterone &#xC544;&#xC138;&#xD14C;&#xC774;&#xD2B8; (DOCA)&#xC5D0;&#xC11C; &#xC0C1;&#xC2B9; &#xB41C; &#xD608;&#xC555;&#xC758; &#xC9C0;&#xC18D;&#xC801;&#xC778;&#xB41C;&#xAC00;-&#xC18C;&#xAE08; &#xC950;. &#xACE0;&#xD608;&#xC555;&#xC740; &#xC7A5;&#xAE30;&#xC801;&#xC778; &#xC9C8;&#xBCD1;, &#xC6B0;&#xB9AC; &#xD604;&#xC7AC; &#xB354; &#xC774;&#xC0C1; (30 &#xC77C;) 5-HT &#xC8FC;&#xC785; &#xC124;&#xB9BD;&#xB41C; &#xACE0;&#xD608;&#xC555; DOCA &#xC18C;&#xAE08; &#xC950;&#xC5D0;&#xC11C; &#xD608;&#xC555;&#xC758; &#xC9C0;&#xC18D;&#xC801;&#xC778;&#xB41C;&#xAC00; &#xC77C;&#xC73C;&#xD0AC; &#xC218; &#xC788;&#xB294; &#xAC00;&#xC124;&#xC744; &#xD14C;&#xC2A4;&#xD2B8;. &#xC774; &#xAE30;&#xAC04; (&sim;4 &#xC8FC;) 5-HT DOCA &#xC18C;&#xAE08; &#xACE0;&#xD608;&#xC555;&#xC758; &#xBC1C;&#xC804;&#xC744; &#xC57D;&#xD654; &#xC218; &#xC788;&#xB294;&#xC9C0; &#xC5EC;&#xBD80;&#xB97C; &#xD14C;&#xC2A4;&#xD2B8; &#xD558;&#xB294; &#xB370; &#xCDA9;&#xBD84; &#xD588;&#xB2E4;. 5-HT (25 &mu;g/kg/min, &#xC0AC;&#xC6B0;&#xC2A4; &#xCE90;&#xB864;&#xB77C;&#xC774;&#xB098;) &#xB610;&#xB294; &#xCC28;&#xB7C9; (Veh)&#xB294; &#xD1B5;&#xD574; &#xC804;&#xB2EC; &#xC0BC; &#xD22C; &#xD38C;&#xD504; (1) &#xC124;&#xB9BD;&#xB41C; DOCA &#xC18C;&#xAE08; &#xC950;&#xC5D0; &#xD55C; &#xB2EC; &#xB3D9;&#xC548; DOCA &#xC18C;&#xAE08;&#xC744; &#xAD00;&#xB9AC; &#xD55C; &#xB2EC; &#xD558; &#xACE0; &#xD608;&#xC555;&#xACFC; &#xC2EC;&#xC7A5; &#xBC15;&#xB3D9; telemetrically &#xCE21;&#xC815;&#xC5D0; &#xB300; &#xD55C; &#xC0AC;&#xC804; (2) Sprague-Dawley &#xC950;. 5-HT &#xC8FC;&#xC785;&#xC758; &#xB9C8;&#xC9C0;&#xB9C9; &#xB0A0;, &#xBB34;&#xB8CC; &#xD608;&#xC18C;&#xD310; &#xD50C;&#xB77C;&#xC988;&#xB9C8; 5 HT &#xB18D;&#xB3C4; 5-HT Veh &#xC0DD;&#xAE34; &#xC950; &#xB300;&#xC5D0;&#xC11C; &#xC0C1;&#xB2F9;&#xD788; &#xB192;&#xC740; &#xB418;&#xC5C8;&#xACE0; &#xD3C9;&#xADE0; &#xB3D9;&#xB9E5; &#xC555;&#xB825;&#xC740; 5 HT &#xC8FC;&#xC785; (135 &plusmn; 4 mmHg vs Veh &#xC0DD;&#xAE34; 151 &plusmn; 7 mmHg)&#xC5D0;&#xC11C; &#xD604;&#xC800; &#xD558; &#xAC8C; &#xB0AE;&#xC740; &#xAC00;&#xB09C;&#xD55C; DOCA &#xC18C;&#xAE08; &#xC950; &#xC124;&#xB9BD;. &#xB300;&#xC870;&#xC801;&#xC73C;&#xB85C;, 5-HT-&#xC8FC;&#xC785; DOCA &#xC18C;&#xAE08; &#xACE0;&#xD608;&#xC555;&#xC758; &#xBC1C;&#xC804;&#xC744; &#xBC29;&#xC9C0; &#xD558;&#xC9C0; &#xC54A;&#xC558;&#xB2E4; (144 &plusmn; 7 mmHg vs Veh = 156 &plusmn; 6 mmHg). &#xB300;&#xB3D9;&#xB9E5; &#xC2A4;&#xD2B8;&#xB9BD;&#xC758; isometric &#xC218;&#xCD95; &#xCE21;&#xC815; &#xD588;&#xB2E4; &#xADF8;&#xB9AC;&#xACE0; &#xC54C;&#xD30C; &#xC544;&#xB4DC;&#xB808;&#xB0A0;&#xB9B0; &#xC218;&#xC6A9; &#xCCB4; &#xAE38; &#xD56D; &#xC81C; phenylephrine (PE) &#xB610;&#xB294; 5-HT&#xB3C4; &#xD798;&#xB3C4; &#xCD5C;&#xB300; &#xC218;&#xCD95; 5-HT (&#xC124;&#xB9BD; &#xB610;&#xB294; &#xC608;&#xBC29; &#xC8FC;&#xC785;)&#xC758; &#xC8FC;&#xC785;&#xC5D0; &#xC758;&#xD574; &#xC218;&#xC815; &#xB41C; &#xBC0F; &#xC544; &#xC138; &#xD2F8; &#xCF5C;&#xB9B0; (ACh)&#xC744; &#xCD5C;&#xB300; &#xB300;&#xB3D9;&#xB9E5; &#xC774;&#xC644;&#xC740; &#xACB8;&#xC190; &#xD558; &#xAC8C; &#xD558;&#xC9C0;&#xB9CC; &#xD558;&#xC9C0; &#xD06C;&#xAC8C; &#xD5A5;&#xC0C1; (&sim;15% &#xAC1C;&#xC120;). &#xC774; &#xC5F0;&#xAD6C;&#xB294; 5 HT&#xC740; &#xD06C;&#xAC8C; &#xC218;&#xC815; &#xD558;&#xC9C0; &#xC54A;&#xB294; &#xB610;&#xB294; &#xC218;&#xC815;&#xB41C; &#xD608;&#xAD00; &#xBC18;&#xC751;&#xC5D0; &#xC758;&#xC874; &#xD558;&#xB294; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC5D0; &#xD55C; &#xB2EC;&#xC5D0; &#xAC78;&#xCCD0; &#xC124;&#xB9BD;&#xB41C; DOCA &#xC18C;&#xAE08; &#xACE0;&#xD608;&#xC555; &#xC950;&#xC5D0;&#xC11C; &#xD608;&#xC555;&#xC744; &#xB0AE;&#xCD94;&#xB294; &#xC218; &#xBCF4;&#xC5EC; &#xC90D;&#xB2C8;&#xB2E4;. &#xC774; &#xCC3E;&#xB294; 5 HT &#xB808;&#xBCA8; &#xC0C1;&#xC2B9; &#xACE0;&#xD608;&#xC555;&#xC758; &#xCE58;&#xB8CC;&#xC5D0; &#xB3C4;&#xC6C0;&#xC774; &#xB420; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4; &#xAC00;&#xB2A5;&#xC131;&#xC744; &#xC5F4;&#xC5B4;.

1 &#xAC1C;&#xC6D4; &#xC138;&#xB85C;&#xD1A0;&#xB2CC; &#xC8FC;&#xC785; &#xACB0;&#xACFC; &#xC7A5;&#xAE30;&#xAC04;&#xB41C; &#xD608;&#xC555; Deoxycorticosterone &#xC544;&#xC138;&#xD14C;&#xC774;&#xD2B8; (DOCA) &#xC18C;&#xAE08; &#xACE0;&#xD608;&#xC555; &#xC950;&#xC5D0;&#xC11C;&#xAC00;.

Una infusi&oacute;n de 7 d&iacute;as de la serotonina (5-Hidroxitriptamina, 5-HT) causa una ca&iacute;da sostenida en la presi&oacute;n arterial elevada en el acetato de hombre deoxycorticosterone (DOCA)-rata sal. Como la hipertensi&oacute;n es una enfermedad a largo plazo, actualmente probamos la hip&oacute;tesis de que una mayor infusi&oacute;n de 5-HT (30 d&iacute;as) podr&iacute;a provocar una ca&iacute;da sostenida en la presi&oacute;n arterial en la rata hipertensa establecido DOCA-sal. Este per&iacute;odo de tiempo (&sim;4 semanas) tambi&eacute;n era suficiente para probar si la 5-HT podr&iacute;a atenuar el desarrollo de la hipertensi&oacute;n de DOCA-sal. 5-HT (25 &mu;g/kg/min; sc) o veh&iacute;culo (Veh) fue entregado mediante bomba osm&oacute;tica a ratas de DOCA-sal (1) establecidas durante un mes, (2) ratas Sprague-Dawley antes de la administraci&oacute;n de DOCA-sal para un mes y la presi&oacute;n arterial y pulso mide telemetrically. En el &uacute;ltimo d&iacute;a de la infusi&oacute;n de 5-HT, plaquetas gratis pobres las concentraciones plasm&aacute;ticas de la 5-HT fueron significativamente superiores en 5-HT versus Veh-infundido de ratas, y la presi&oacute;n arterial media fue significativamente menor en 5-HT-infundido (135 &plusmn; 4 mmHg vs Veh-infundido 151 &plusmn; 7 mmHg) establecieron ratas DOCA-sal. Por el contrario, 5-HT-infusi&oacute;n no impidi&oacute; el desarrollo de la hipertensi&oacute;n de DOCA-sal (144 &plusmn; 7 mmHg vs Veh = 156 &plusmn; 6 mmHg). Se midi&oacute; la contracci&oacute;n isom&eacute;trica de tiras a&oacute;rticas, ni la potencia ni la m&aacute;xima contracci&oacute;n para el receptor adren&eacute;rgico alfa agonista fenilefrina (PE) o 5-HT fueron modificados por la infusi&oacute;n de 5-HT (infusi&oacute;n establecida o preventiva) y m&aacute;xima relajaci&oacute;n a&oacute;rtica a acetilcolina (ACh) fue modesto pero no significativamente mejorado (&sim;15% mejora). Este estudio demuestra la 5-HT es capaz de bajar la presi&oacute;n arterial en establecido ratas hipertensas de DOCA-sal a lo largo de un mes en un mecanismo que no modifica significativamente o depende de la respuesta vascular modificado. Este hallazgo abre la posibilidad de que la elevaci&oacute;n de los niveles de 5-HT podr&iacute;a ser &uacute;til en el tratamiento de la hipertensi&oacute;n.

Resultados de infusi&oacute;n de serotonina de un mes en una prolongada ca&iacute;da en la presi&oacute;n arterial en ratas hipertensas sal Deoxycorticosterone acetato (DOCA).

Venous function is underappreciated in its role in blood pressure determination, a physiologic parameter normally ascribed to changes in arterial function. Significant evidence points to the hormone endothelin-1 (ET-1) as being important to venous contributions to blood pressure. We hypothesized that the artery and vein should similarly depend on the signaling pathways stimulated by ET-1, specifically phospholipase C (PLC) activation. This produces two functional arms of signaling: diacylglycerol (DAG; protein kinase C [PKC] activation) and inositol trisphosphate (IP3) production (intracellular calcium release).

Nathan R. Tykocki

Department of Pharmacology

University of Vermont College of Medicine

Measurement of Smooth Muscle Function in the Isolated Tissue Bath-applications to Pharmacology Research

Nathan R. Tykocki

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Pharmacology

University of Vermont College of Medicine

Measurement of Smooth Muscle Function in the Isolated Tissue Bath-applications to Pharmacology Research

Department of Pharmacology