The immediate pressor response to saralasin in man: evidence against sympathetic activation and for intrinsic angiotensin II-like myotropism.
The cardiovascular and hormonal effects of intravenous saralasin (0.5, 1 and 5 micrograms min-1 kg-1) were assessed in nine tetraplegic patients (with complete cervical spinal cord transaction above the sympathetic outflow) and in six normal subjects. In the tetraplegic patients, saralasin caused an immediate transient pressor response which was not dose-dependent and substantially greater than the pressor response in normal subjects. The pressor response in the tetraplegic patients was not accompanied by a rise in levels of plasma noradrenaline. In the tetraplegic patients, after alpha-adrenoceptor blockade with thymoxamine (1 mg kg-1 h-1), twice the dose of intravenous noradrenaline was needed to induce the same pressor response. The pressor response to saralasin (5 micrograms kg-1 min-1), however, was unaffected by thymoxamine. Saralasin caused minimal changes in levels of plasma renin activity and plasma aldosterone in both groups. There was no relationship between basal plasma renin activity and the pressor response in either group. We therefore conclude that the immediate transient pressor response to saralasin in man is not due to central sympathetic stimulation, is unlikely to be due to peripheral sympathetic activation and is probably the result of intrinsic angiotensin II-like myotropism.
D000328:Adult; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D013948:Moxisylyte / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D011782:Quadriplegia / Q000503:physiopathology; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology*
D000450:Aldosterone; D012083:Renin; D012504:Saralasin; D013948:Moxisylyte; D009638:Norepinephrine