Reduced chronotropic responsiveness of the heart in experimental uremia

Abstract

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.

Nonhypotensive dose of β-adrenergic blocker ameliorates capillary deficits in the hearts of rats with moderate renal failure

“…On the other hand, there is evidence of diminished β-adrenergic responsiveness [20,30,33], as evidenced by measurements of receptor binding, of postreceptor signaling steps and of the HR response in SNX after stimulation with isoproterenol. α-Adrenoreceptor responsiveness of peripheral vessels is decreased as well [39].…”

Cardiac hypertrophy in neonatal nephrectomized rats: the role of the sympathetic nervous system

“…Sympathetic tone is consistently raised in patients with ESRD, and CV mortality of these patients is dependent on the level of sympathetic nerve system (SNS) overactivity [4]. Studies in adult uremic rats have revealed that increased SNS activity can either decrease or have no effect on adrenergic receptors [5][6][7]. In the adult, β-adrenergic receptor blockade or the destruction of neuronal inputs to β-adrenergic receptors results in compensatory suprasensitivity of receptor signaling and eventually to upregulation of cell-surface receptors [8].…”

Chronic Kidney Disease and Sudden Death: Strategies for Prevention

“…In chronic uremic rats, the density of · 1 and · 2 receptors in the cerebral cortex was significantly increased, while the ß-adrenergic and muscarinergic receptors in the heart as well as cardiac · 1 adrenoceptors were unchanged [18][19][20]. Studies in uremic rats also show variable decreases in contraction of isolated myocytes along with a decrease in the velocity of shortening and relaxation [21][22][23]. Both energy production and consumption are influenced by uremia [24][25][26].…”