The antihypertensive profile of the angiotensin AT1 receptor antagonist GR138950 and the influence of potential homeostatic compensatory mechanisms in renal hypertensive rats

摘要

class="enumerated" style="list-style-type:decimal">The cardiovascular profile of the angiotensin AT1 receptor antagonist, , and the influence of potential compensatory homeostatic mechanisms on this profile, were investigated in renal artery ligated hypertensive (RALH) rats. caused a marked reduction in blood pressure associated with immediate tachycardia in conscious RALH rats. The antihypertensive action of appeared biphasic; an immediate fall in blood pressure, which plateaued within 1 h, and which was followed by a further slow decline that reached maximum between 5–7 h after administration.The tachycardia caused by was attenuated by atenolol and was abolished by combined pretreatment with atenolol and atropine methyl nitrate. However, the antihypertensive profile of was unchanged by these pretreatments.The resting blood pressure and the antihypertensive effect of , in RALH rats, were unaffected by the vasopressin V1 receptor antagonist, [β-mercapto-β,β-cyclopentamethylene propionyl¹-O-Me-Tyr²,Arg⁸]-vasopressin. Thus, vasopressinergic mechanisms are not involved in either maintaining blood pressure in RALH rats, or in compensating for the fall in blood pressure caused by .In anaesthetized RALH rats, caused a marked fall in blood pressure that was accompanied by an increase in heart rate along with sustained increases in renal and splanchnic sympathetic nerve activity.In summary, the biphasic fall in blood pressure evoked by in RALH rats can not be explained on the basis of changes in autonomic control of the heart, alteration of vasopressin-mediated vasoconstrictor mechanisms or overall suppression of central sympathetic outflow. Rather, increased vasoconstrictor tone might serve to oppose the initial fall in blood pressure.