Renal vascular responses to saralasin in conscious chemically denervated rabbits and patients with tetraplegia.
To determine the relative contributions of direct angiotensin-II-like myotropism and sympathetic nerve stimulation to the partial agonist effect of saralasin, the renal vascular responses to i.v. saralasin (5, 10, 20 micrograms/kg/min) were assessed in normal conscious rabbits before and after sympatholytic treatment with guanethidine (24 mg/kg/day for 9 days) and in 6 chronic tetraplegic patients (0.5, 1, 5 micrograms/kg/min) before and after alpha-adrenoreceptor blockade with i.v. thymoxamine (1 mg/kg/h). In rabbits saralasin reduced effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), and increased renal vascular resistance (RVR) without affecting mean arterial blood pressure (BP). Responses were similar in both groups, but recovery following saralasin was more prolonged after treatment with guanethidine. When 0.1 microgram/kg/min (one fiftieth of the smallest i.v. dose) was infused just proximal to the renal arteries in 4 conscious rabbits (chronically cannulated), renal perfusion fell and RVR increased. In tetraplegics saralasin produced a transient rise in BP and variable increase in RVR; neither response being altered by thymoxamine. These results suggest that saralasin-induced renal vasoconstriction is independent of central and peripheral sympathetic activation, and is probably due to an intrinsic angiotensin-II-like myotropic action.
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D003243:Consciousness; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006145:Guanethidine; D006801:Humans; D008297:Male; D013948:Moxisylyte / Q000494:pharmacology; D011782:Quadriplegia / Q000503:physiopathology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D012504:Saralasin / Q000494:pharmacology*; D013563:Sympathectomy, Chemical; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000804:Angiotensin II; D012504:Saralasin; D013948:Moxisylyte; D006145:Guanethidine