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Seven patients with severe orthostatic hypotension due to peripheral autonomic neuropathy were studied., In four patients, heart rate did not change after the β-adrenoceptor antagonists propranolol or metoprolol. After the partial β-adrenoceptor agonist pindolol heart rate rose in a dose-dependent manner. After α-adrenoceptor antagonists phentolamine and yohimbine heart rate and blood pressure did not change, which confirmed that these patients were indeed sympathetically denervated., The non-selective β-adrenoceptor agonist isoprenaline and the β2-selective β-adrenoceptor agonist salbutamol increased heart rate and lowered arterial pressure, whereas the β1-adrenoceptor agonist prenalterol increased both heart rate and arterial pressure. After treatment with pindolol, the patient was desensitized for the chronotropic effects of the β-adrenoceptor agonists in the order: salbutamol > isoprenaline > prenalterol. The desensitization of the depressor effects of the β-adrenoceptor agonists was in the order isoprenaline > salbutamol. These data suggest preferential cardiovascular β2-adrenoceptor sensitization in patients with chronic autonomic failure, which can be reversed by treatment with pindolol. They also provide in vivo evidence for the existence of cardiac chronotropic β2-adrenoceptors in man., The α-adrenoceptor agonists methoxamine, phenylephrine, noradrenaline, clonidine and guanfacine increased arterial pressure. The vascular reactivity for the different α-adrenoceptor agonists differed markedly, as was shown by the declining steepness of the dose-response curves in the order methoxamine and phenylephrine > noradrenaline > clonidine > guanfacine. The pressor profiles of these agonists were also different. These data suggest, that different α-adrenoceptor populations are involved in the contractile responses to these α-agonists, being methoxamine and phenylephrine a1, noradrenaline α1 > α2 and clonidine and guanfacine α2 > α1., Two patients were treated with clonidine, slow release, 250 μg daily, which increased supine and standing arterial pressure and relieved orthostatic symptoms. In one patient the pressor-depressor response to adrenaline was converted to a pure pressor response after clonidine, which contrasted with a pure pressor response to adrenaline after treatment with pindolol. Treatment with clonidine shifted the dose-response curves of the α-adrenoceptor agonists in the order clonidine > noradrenaline > phenylephrine, suggesting preferential α2-adrenoceptor desensitization by clonidine in this patient., These data provide further evidence for the view that α1-β1 and α2-β2-adrenoceptor sensitivity and/or responsiveness are independently regulated and lend support to the hypothesis that peripheral α2-β2-adrenoceptors are not innervated. [ABSTRACT FROM AUTHOR]