Regional hemodynamic effects of endothelin-2 and sarafotoxin-S6b in conscious rats.
Regional hemodynamic responses to bolus doses (4 and 40 pmol) and 60-min infusions (12 and 120 pmol/h) of endothelin-2 (ET-2) and sarafotoxin-S6b (S6b) were measured in conscious Long-Evans and Brattleboro rats chronically instrumented with pulsed Doppler flow probes. In both strains of rat the two bolus doses of ET-2 and S6b peptides caused an initial fall in mean blood pressure (MBP). At the higher dose S6b caused a greater fall in MBP than ET-2. In Long-Evans rats the fall in MBP after S6b was associated with renal, mesenteric, and hindquarters vasodilatations; in Brattleboro rats there was no renal or mesenteric vasodilatation with S6b. The high dose of ET-2 caused early mesenteric vasoconstriction in both strains. After the initial fall in MBP there were dose-dependent increases in MBP together with renal and mesenteric vasoconstrictions. These effects were generally greater after S6b than after ET-2 and no less marked in Brattleboro than in Long-Evans rats, indicating that release of endogenous vasopressin was not an indispensable component of the response. Infusions of the higher dose of ET-2 or S6b caused increases in MBP only, associated with renal, mesenteric, and hindquarters vasoconstrictions. The results indicate that S6b is a more potent stimulus than ET-2 of vasodilator mechanisms in vivo; despite this, S6b also exerts more marked vasoconstrictor effects than ET-2.
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, United Kingdom.
S M
SM
Gardiner
A M
AM
Compton
T
T
Bennett
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply*; D007275:Injections, Intravenous; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011910:Rats, Brattleboro / Q000502:physiology; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D013152:Splanchnic Circulation / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology*
D016232:Endothelins; D010455:Peptides; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6