Effects of prazosin and clonidine on sympathetic and baroreflex function in patients with essential hypertension

Prazosin, a peripherally active alpha-adrenoceptor antagonist, and clonidine, a centrally active alpha-adrenoceptor agonist, both reduce blood pressure but with different alterations in sympathetic nervous system activity. We studied the effects of monotherapy with either prazosin or clonidine in 10 and 30 patients, respectively, with essential hypertension. Prazosin reduced blood pressure without affecting heart rate or circulating plasma catecholamines. Sensitivity to injected phenylephrine was markedly reduced by prazosin, and sensitivity to isoproterenol was increased, whereas baroreflex sensitivity was not significantly altered. Blood pressure response to prazosin was correlated with basal plasma norepinephrine concentration (r = 0.64, P less than 0.04). In contrast, clonidine reduced heart rates and plasma concentrations of both norepinephrine and epinephrine, increased the sensitivity to phenylephrine, and increased baroreflex sensitivity. Blood pressure response to clonidine was correlated with reduction in plasma norepinephrine concentration (r = 0.51, P less than 0.004). Thus, blood pressure reduction resulting from monotherapy with either prazosin or clonidine occurs through different antisympathetic effects, suggesting that combined therapy might be useful in those unresponsive to either drug alone.