Modulation of noradrenergic but not angiotensinergic blood pressure control by ?? -blockade with carteolol

Various β -blockers possessing similar antihypertensive potency have been found to differ widely with regard to their influence on blood pressure-regulating factors such as cardiac output and plasma levels of renin or norepinephrine. Recently, P-blocker-induced stimulation of circulating atrial natriuretic factor (ANF) was reported. Blood pressure is determined not only by levels of vasoconstrictive factors but also by tissue reactivity. To investigate these aspects, we assessed the cardiovascular responsiveness to norepinephrine and angiotensin II, plasma levels of catecholamines, angiotensin II, ANF and aldosterone and the body sodium-blood volume state of 15 patients with essential hypertension (mean ageis.e.m., 42 ± 3 years) and 12 normal control subjects (41 ± 5 years), first on placebo and then after 4 weeks of intervention with carteolol, a non-selective p-adrenergic antagonist with intrinsic sympathomimetic activity. Compared with placebo, carteolol decreased resting plasma norepinephrine in both groups while plasma norepinephrine-blood pressure response curves were shifted to the left, their slopes increased and norepinephrine pressor doses decreased (P<0.05 to<0.001). Chronotropic responses to isoproterenol were abolished but negative chronotropic responses to a norepinephrine-induced 20 mmHg rise in diastolic blood pressure were unaltered. Plasma norepinephrine clearance in the supine position was slightly decreased in hypertensive and unchanged in normal subjects. Supine and upright blood pressure was lowered (P<0.05 to 0.001) in the hypertensive while upright systolic blood pressure only decreased in the normal group. Carteolol did not modify supine and upright plasma dopamine, ANF, renin, angiotensin II and aldosterone levels, plasma angiotensin II—blood pressure response and plasma angiotensin—aldosterone response curves, plasma angiotensin II clearance, exchangeable body sodium, plasma or blood volumes. These findings indicate that p-blockade with carteolol modifies noradrenergic blood pressure control in both normal and essential hypertensive subjects, but is largely neutral with regard to plasma angiotensin ll-mediated blood pressure and aldosterone regulation, plasma ANF, dopamine and the body sodium-blood volume state. Therefore, the antihypertensive action of this β -blocker most probably involves a decrease in sympathetic outflow which may, in turn, downregulate a norepinephrine-dependent 'slow* pressor mechanism.