Cardiac chronotropic responses to isoprenaline, carbachol and electrical stimulation of the cervical sympathetic and vagal nerves were recorded in rats with glycerol-induced acute renal failure (ARF) and control rats. The experiments involving electrical stimulation of cardiac nerves were performed in rats which either had been pretreated with indomethacin (1 mg kg-1 twice daily for 2 days) or had undergone acute bilateral renal pedicle ligation. The findings from this investigation indicate that the reduced chronotropic responses to vagal stimulation in rats with glycerol-induced ARF are due to a reduction in acetylcholine release mediated by prostaglandins possibly originating from the damaged kidneys. The diminished response to cervical sympathetic stimulation results from a decreased postsynaptic response to beta-adrenoceptor stimulation.

Cardiovascular responses were determined in rats with chronic renal failure (CRF) produced by five sixths nephrectomy and in sham-operated rats. The conscious systolic blood pressure of rats with CRF was significantly higher than the pressure in controls although, after anaesthesia, there were no significant differences in the mean arterial pressure between the two groups of rats. The pressor responses to noradrenaline in rats with CRF were not significantly different from those recorded in sham-operated controls. The bradycardia elicited by electrical stimulation of the vagus nerve was significantly diminished in rats with CRF. However, indomethacin treatment (1 mg kg-1 s.c. twice daily for 2 days) abolished the differences in response to vagal stimulation. Changes in heart rate in response to electrical stimulation of the cervical sympathetic nerve and to bolus i.v. injections of isoprenaline and carbachol were similar in rats with CRF and controls. The most notable disturbance of cardiovascular function in rats with CRF is the diminished cardiac chronotropic response to vagal stimulation which appears to be mediated by a presynaptic action of prostaglandins.

Cardiac reactivity has been determined in rats with acute renal failure (ARF) induced by either bilateral nephrectomy or intramuscular glycerol injection. Rats with bilateral nephrectomy showed reduced chronotropic responses to cervical sympathetic stimulation but no appreciable alteration in the chronotropic responses to vagal stimulation. By contrast, we have previously noted that rats with glycerol-induced ARF show diminished chronotropic responses to stimulation of both nerves. The negative chronotropic and inotropic responses to carbachol in isolated atria from both nephrectomized and glycerol-injected rats were not significantly different from their respective controls. In both models of ARF the atrial positive chronotropic responses to isoprenaline were significantly decreased whilst positive inotropic responses were not significantly different from controls. The results indicate that the cause of the reduced chronotropic response to vagal stimulation observed in glycerol-injected rats is of presynaptic origin whilst the reduced chronotropic response to cervical sympathetic stimulation noted in both models of ARF may be due to an impaired postsynaptic response.

Vascular reactivity in-vivo and in-vitro was examined in rats with acute renal failure produced by bilateral nephrectomy or intramuscular glycerol injection. Bilaterally nephrectomized rats displayed enhanced pressor responses to noradrenaline and angiotensin. However, the contractile responses to noradrenaline, angiotensin and potassium chloride of aortic rings and portal vein segments from nephrectomized rats were not significantly different from the responses obtained in vessels from sham-operated controls. Rats with glycerol-induced ARF which were pretreated with indomethacin had significantly lower pressor responses to noradrenaline and angiotensin than similarly treated control animals. Aortic rings from glycerol-injected rats produced significantly smaller contractions to noradrenaline than preparations from controls. This difference was not abolished by incubation of vessels with indomethacin. The findings suggest that the absence of kidneys or the presence of damaged renal tissue and not uraemia itself have pronounced but opposite effects on vascular reactivity. The depression of vascular reactivity in glycerol-induced ARF does not appear to be a result of increased production of prostaglandins.