Estimation of angiotensin II receptor activity in chronic congestive heart failure.
The renin-angiotensin system has been shown to participate in the pathophysiology of chronic heart failure in many patients. However, the immediate assessment of this contribution in individual patients may sometimes be difficult. As a pharmacologic estimate of angiotensin II receptor activity, we infused the angiotensin II analogue, saralasin, in 20 patients with severe chronic congestive heart failure (CHF). The infusion resulted in blood pressure responses ranging from an agonist pressor response (increased systemic resistance) in patients with low intrinsic renin-angiotensin system activity, to an antagonist depressor response (decreased systemic resistance) in patients with marked activation of the renin-angiotensin system. The ability of the saralasin response to pharmacologically estimate angiotensin II receptor activity in CHF was further revealed by two physiologic maneuvers that decrease endogenous circulating angiotensin II and angiotensin II receptor occupancy. Both converting enzyme inhibition with captopril and sodium repletion, factors known to decrease endogenous angiotensin II activity, provoked agonist responses to saralasin infusion. Furthermore, saralasin was able to reverse the orthostatic hypotension precipitated by converting enzyme inhibition of angiotensin-dependent vascular tone. In summary, saralasin provided a means to estimate angiotensin receptor activity and may therefore serve as a probe of angiotensin-mediated vasoconstriction in the pathophysiology of chronic CHF.
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril / Q000494:pharmacology; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000201:enzymology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007024:Hypotension, Orthostatic / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011945:Receptors, Angiotensin / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D002216:Captopril; D012964:Sodium; D012083:Renin; D012504:Saralasin