Inhibition of angiotensin II potentiation of sympathetic nerve activity by beta-adrenergic antagonists.
Since beta-adrenergic blockers are effective in the therapy of hypertension by a mechanism related to the degree of activation of the renin-angiotensin system, the effect of eight beta blockers was examined on angiotensin II potentiation of nerve stimulation (NS) in isolated perfused rat mesenteric vessels. The vasoconstrictor response to periarterial NS was obtained by monitoring changes in perfusion pressure while a beta blocker or a beta blocker and angiotensin II (3 ng/ml) were added to the perfusate. Although each beta blocker tended to decrease responses to NS, in the concentrations used, only metoprolol significantly inhibited responses to NS. Angiotensin II, when infused alone, potentiated the responses to NS by 63% (p less than 0.01). These enhanced responses following angiotensin II were inhibited in a dose-related manner (10--300 ng/ml) by beta 1, beta 2, and mixed beta blockers. At the 100 ng/ml concentration, DL-propranolol, timolol, metoprolol, practolol, butoxamine, and H35/25 inhibited the angiotensin II potentiation of NS by 83%, 76%, 77%, 59%, 72%, and 41% respectively. The order of potency for this action was as follows: timolol = metoprolol = butoxamine greater than propranolol greater than practolol greater than H35/25. Administration of D- and L-propranolol also reduced the responses by 75%. The vasoconstrictor responses to injected norepinephrine (NE), in the presence and absence of angiotensin II, were not altered by DL-propranolol or timolol. In conclusion, beta-adrenergic blockers were found to interfere with the effect of angiotensin II on the sympathetic neuron, a property that could contribute to the antihypertensive action of these drugs.