Beta-adrenergic activation of the renin-angiotensin system following alpha 2-, alpha 1-, or nonselective alpha-blockade in conscious dogs: no relation to the changes in blood pressure.

We analyzed the role of the renin-angiotensin system following alpha 2-, alpha 1-, or nonselective alpha-blockade in an intact organism in which both postsynaptic alpha-adrenoceptor types contribute to adrenergic vasoconstriction. In conscious dogs, alpha 2-blockade (0.3 mg/kg rauwolscine, n = 10) increased mean arterial pressure by 40 mm Hg, while hypotension by 8 mm Hg occurred following nonselective alpha-blockade (1.5 mg/kg phentolamine, n = 9) and by 20 mm Hg following alpha 1-blockade (1.2 mg/kg prazosin, n = 10). Plasma angiotensin II (pg/ml) rose by 103 +/- 28 (SEM), 143 +/- 48, and 58 +/- 15 following alpha 2-, nonselective alpha-, or alpha 1-blockade, respectively. While alpha 2- or nonselective alpha-blockade induced tachycardia and substantial elevations of plasma catecholamines, alpha 1-blockade did not. Beta-Blockade (2 mg/kg nadolol) attenuated the elevations of angiotensin following alpha 2- or nonselective alpha-blockade by 100 and 88%, respectively, without affecting the alpha 1-blockade-induced elevation, which is mainly mediated by the hypotension. Pretreatment with 3 mg/kg captopril reduced the pressure increase induced by alpha 2-blockade from 40 to 13 +/- 10 mm Hg and aggravated the decline in blood pressure induced by nonselective alpha-blockade from 8 to greater than 50 mm Hg. In anesthetized, spinalized dogs, both types of alpha-blockade competitively antagonized the pressor effect of the alpha 2-agonist azepexole by the same degree. It is concluded that, in the intact animal, the central and peripheral presynaptic augmentation of sympathoexcitation induced by alpha 2- or nonselective alpha-blockade leads to a strong beta-adrenergic activation of the renin-angiotensin system, independent of the concomitant changes in blood pressure. The constrictive action of the activation contributes substantially to the compensation of the vascular adrenoceptor blockade induced by nonselective or alpha 2-selective blockade in the intact organism.