Winquist R J, Scott A L, Vlasuk G P
Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Hypertension. 1989 Jul;14(1):111-4. doi: 10.1161/01.hyp.14.1.111.
Intravenous (bolus) administration of endothelin results in a transient fall in blood pressure that is accentuated in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto normotensive rats (WKY). In attempting to discern possible mechanisms underlying this depressor response, we examined the ability of endothelin to release atrial natriuretic factor (ANF) from isolated, spontaneously contracting atria from SHR and WKY. Isolated right atria were suspended under 3.0 g of resting force in tissue baths with the amount of immunoreactive ANF (irANF) released after exposure to endothelin assessed by radioimmunoassay. Endothelin (10(-8) and 10(-7) M) caused a concentration-dependent increase (1.5-4.5-fold) in the release of irANF, which was significantly greater in atria of SHR compared with WKY. The greater release of irANF in atria of SHR versus WKY was not related to tissue weight or changes in contractile rate or force induced by endothelin. Therefore, endothelin appears to cause a direct release of irANF from rat right atria in vitro. As found for the depressor response in vivo, endothelin is more efficacious in the hypertensive compared with the normotensive atrial preparation. Release of ANF may be important in the hypotensive response to endothelin in vivo.
静脉（推注）给予内皮素会导致血压短暂下降，与Wistar-Kyoto正常血压大鼠（WKY）相比，自发性高血压大鼠（SHR）的这种血压下降更为明显。为了探究这种降压反应背后可能的机制，我们检测了内皮素从SHR和WKY分离的自发性收缩心房中释放心房利钠因子（ANF）的能力。将分离的右心房在组织浴中以3.0 g的静息张力悬挂，通过放射免疫测定法评估暴露于内皮素后释放的免疫反应性ANF（irANF）量。内皮素（10^(-8)和10^(-7) M）导致irANF释放呈浓度依赖性增加（1.5至4.5倍），与WKY相比，SHR心房中的增加更为显著。SHR心房中irANF的释放量高于WKY，这与组织重量、内皮素诱导的收缩速率或力量变化无关。因此，内皮素似乎在体外可直接从大鼠右心房释放irANF。正如在体内降压反应中所发现的，与正常血压的心房制剂相比，内皮素在高血压心房制剂中更有效。ANF的释放可能在体内对内皮素的降压反应中起重要作用。
