| The purpose of the study was to investigate the in vivo and in vitro hemodynamical effects of endothelin(ET) in spontaneously hypertensive rats(SHR) and wistar — kyoto rats(WKY) and their modification by various factors, so as to understand its rote in cardiovascutar regulation.Subjects of the study consisted of male SHR, stroke prone SHR(SHRSP). WKY and a few Wistar rats of different ages. The study was carried out in two ways: the in vivo hemodynamical study and the perfusion study of isolated hearts.In the in vivo study, the effects of ET on blood preessure(BP) . heart rate(HR), and dp/dt were first examined in age-matched SHR and WKY of three age groups(12 wks, 8/8; 24wks 8/7; 36wk 5/7). It was demonstrated that F.T induced biphasic change of BP in both SHR and WKY, i.e. an initial transient reduction followed by prolonged elevation. SHR displayed greater depressor response and lesser pressor reponse as compared with WKY of the same age, and the difference was preserved with the second dose of ET, which was given 120 minuled later. ET caused minimal change in HR, transient depression of dp/dt and occasional pre mature beats of ventricular origin. To further explore the mechanisms for the difference, additional drug- pretreatment study was done, which showed that while pretreatment with angiotensin-converting enzyme inhibitor(ACEI) or high salt intake (1% Nacl) had insignificant effects on ET-induced BP response,ganglion-blocker greatly enhanced its pressor response and n(?)enunled the depresson response. Also, the plasma levels of 6-keto-PGF1a, which was sampled 2 minutes after i.v. ET( 1 nmol/kg), was found higher in SHR than in WKY. It isbelieved that although ET is a potent vasoconstictor in vitro and in vivo...
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