Hypoxia uniquely potentiates the inotropic effects of angiotensin II analogues in cat papillary muscles, in contrast to the depressed response seen with ouabain and norepinephrine.
The effects of several inotropic agents were investigated in papillary muscle preparations from normal cats and cats that had undergone previous total extrinsic cardiac denervation. The papillary muscles were bathed in a modified Krebs-Ringer's solution which was equilibrated with 95% O 2 -5% CO 2 for the control drug studies or 5% O 2 -5% CO 2 -90% N 2 for the hypoxia studies. This degree of hypoxia produced a 32 ± 3% decrease in tension in papillary muscles from normal cats and a 14 ± 4% decrease in catecholamine-depleted papillary muscles. During hypoxia there was depression of the maximum response to ouabain and norepinephrine with otherwise unchanged dose-response curves. Deterioration of the hypoxic muscles occurred after exposure to norepinephrine concentrations of 5 x 10 -7 M and greater. The dose-response curve for angiotensin II was unchanged by hypoxia. However, during hypoxia, the dose-response curves for two heptapeptide analogues of angiotensin II, 1-des-5-Valand 1-des-5-Ile-angiotensin II, were augmented. The inotropic effects of these analogues under control and hypoxic conditions were the same in the normal and catecholamine-depleted muscles. The potentiation by hypoxia of the inotropic effects of the angiotensin II analogues is unique among the agents studied.
Kent et al. (Tue,) studied this question.