Reduced chronotropic responsiveness of the heart in experimental XXXX .

@entity6306 @entity30828 @entity5507 @entity30049 @entity3044 @entity3897 @entity35 @entity1928
Cardiac beta-adrenoceptor responsiveness was evaluated in experimental @entity5507 by in vivo and in vitro techniques. @entity5507 was induced in @entity35 by bilateral nephrectomy for 48 h. In @entity35 with chronic intra-arterial and intravenous catheters, cardiovascular reflexes and the renin-angiotensin system were blocked with @entity3897 , @entity30049 , and a converting-enzyme inhibitor, respectively. Blood pressure (BP) and heart rate (HR) were continuously recorded. Cumulative doses of @entity3044 were injected intravenously. In uremic @entity35 , the dose-response curve for the HR response showed a lower maximal response (P less than 0.01) and no significant difference in 50% effective dose values compared with controls, whereas the BP decrease caused by @entity3044 was similar in control and uremic @entity35 . When @entity1928 was injected intravenously to stimulate adenylate cyclase in a receptor-independent manner, the maximal HR increase was lower in uremic @entity35 (P less than 0.01). beta-Adrenoceptor density and affinity, measured by 125I- @entity30828 binding to sarcolemmal membranes, was not different between control and uremic @entity35 . Also binding affinities for the agonist @entity3044 were not different between groups. Basal adenylate cyclase activity, as well as activity after maximal stimulation by @entity3044 and by @entity1928 were lower in uremic than in control @entity35 (P less than 0.01). The results show that the chronotropic response of the heart is reduced in @entity5507 . Such @entity6306 may be due, at least in part, to a reduced activity of cardiac adenylate cyclase.
