AJP - Heart and Circulatory Physiology, Vol 250, Issue 5 846-H852, Copyright © 1986 by American Physiological Society
Reduced chronotropic responsiveness of the heart in experimental uremia
J. F. Mann, K. H. Jakobs, J. Riedel and E. Ritz
Cardiac beta-adrenoceptor responsiveness was evaluated in experimental
uremia by in vivo and in vitro techniques. Uremia was induced in rats by
bilateral nephrectomy for 48 h. In rats with chronic intra-arterial and
intravenous catheters, cardiovascular reflexes and the renin-angiotensin
system were blocked with atropine, pentolinium, and a converting-enzyme
inhibitor, respectively. Blood pressure (BP) and heart rate (HR) were
continuously recorded. Cumulative doses of isoproterenol were injected
intravenously. In uremic rats, 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 isoproterenol was similar in control and uremic rats.
When forskolin was injected intravenously to stimulate adenylate cyclase in
a receptor-independent manner, the maximal HR increase was lower in uremic
rats (P less than 0.01). beta-Adrenoceptor density and affinity, measured
by 125I-cyanopindolol binding to sarcolemmal membranes, was not different
between control and uremic rats. Also binding affinities for the agonist
isoproterenol were not different between groups. Basal adenylate cyclase
activity, as well as activity after maximal stimulation by isoproterenol
and by forskolin were lower in uremic than in control rats (P less than
0.01). The results show that the chronotropic response of the heart is
reduced in uremia. Such hyporesponsiveness may be due, at least in part, to
a reduced activity of cardiac adenylate cyclase.
