Regional hemodynamic effects of antihypertensive renomedullary lipids in conscious rats.

Abstract

Renomedullary tissue has been proposed to exert an antihypertensive endocrine-like action. The antihypertensive polar renomedullary lipids (APRL) and neutral renomedullary lipids (ANRL) are potential mediators of this action. The blood pressure and regional hemodynamic responses to APRL administered peripherally (i.v.) and to the central nervous system (CNS) was evaluated in normal rats and rats with sinoaortic deafferentation (SAD) to remove baroreflex buffering. Rats were chronically instrumented with Doppler flow probes for measurement of mesenteric, renal and hind-quarter vascular resistance, with arterial pressure and i.v. catheters and with lateral cerebroventricular cannuli for intracerebroventricular (i.c.v.) administration. I.v. APRL (0.01-1.0 .mu.g) produced a dose-dependent decrease in blood pressure, tachycardia, and dilation of all vascular beds studied. The dose-response relationships were shifted to the left in SAD animals. APRL administered i.c.v. had no effect on intact or SAD rats. Pressor and regional vasoconstrictor responses to norepinephrine, angiotensin and vasopressin were markedly reduced in SAD animals during constant infusion of APRL. In a 2nd group of conscious SAD animals instrumented for blood pressure and heart rate measurements, i.v. ANRL (500.mu.g) decreased both arterial pressure (-45 .+-. 16 mm Hg) and heart rate (- 50 .+-. 16 bpm [beats/min]). When given i.c.v., however, ANRL (10-100 .mu.g) had no significant effect on resting blood pressure or heart rate. APRL and ANRL apparently produce no significant cardiovascular effects that are mediated through the CNS. However, both lipids are potent depressor agents, and APRL exhibits a strong peripheral vasodilator action and nonspecifically reduces reactivity to vasoconstrictor agents.