Angiotensin II and noradrenergic transmission in the pithed rat.
The norepinephrine (NE) release rate, determined in the pithed rat with stimulated sympathetic outflow (3 Hz), was calculated from the steady-state concentrations of endogenous NE and [3H]NE in the central venous pool after infusion of [3H]NE intraarterially (i.a.). This technique appropriately corrects for NE metabolism and disposition since the [3H]NE closely follows the removal path of neuronally released NE. Infusion of angiotensin II (AII) [0.1 microgram/kg/min, intravenously (i.v.)] failed to increase the NE release rate. A higher rate of infusion of AII (1.0 microgram/kg/min, i.v.) markedly increased the NE release rate. The converting enzyme inhibitor captopril (1 mg/kg, i.v.) and the AII-receptor blocking drug saralasin (10 micrograms/kg/min, i.v.) decreased the NE release rate, indicating a tonic activation of facilitatory prejunctional AII receptors at sympathetic nerve endings. After bilateral nephrectomy, captopril and saralasin did not decrease the NE release rate. This suggests that renin release from the kidney is the primary determinant of AII effects and that local tissue generation of AII is not important Other differences were observed in nephrectomized rats: AII (0.1 microgram/kg/min, i.v.), in contrast to its lack of effect in rats with kidneys, increased the NE release rate. This suggests that the lack of effect of AII (0.1 microgram/kg/min, i.v.) on NE release in rats with kidneys may occur because facilitatory prejunctional AII receptors are maximally activated by endogenous AII.
Majewski
H
H
Department of Pharmacology, University of Melbourne, Victoria, Australia.
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D003655:Decerebrate State; D003891:Desipramine / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D009392:Nephrectomy; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012504:Saralasin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D000804:Angiotensin II; D002216:Captopril; D012504:Saralasin; D003891:Desipramine; D009638:Norepinephrine; D004837:Epinephrine