Beta adrenoceptor facilitation of norepinephrine release is not dependent on local angiotensin II formation in the rat isolated kidney.
The aim of the study was to investigate beta adrenoceptor modulation of norepinephrine release from sympathetic nerves in rat isolated kidney. After preincubation with [3H]norepinephrine, the renal nerves were stimulated at 1 Hz. The stimulation induced (S-I) outflow of radioactivity was taken as an index of norepinephrine release. Isoproterenol (0.1 microM) enhanced the S-I outflow of radioactivity. This effect was abolished by the beta-2 adrenoceptor blocking drug ICI 118551 (0.1 microM) but unaltered by the beta-1 adrenoceptor blocking drug atenolol (0.3 microM). In the presence of a high concentration of the angiotensin converting enzyme inhibitor captopril (5 microM), isoproterenol failed to enhance the S-I outflow of radioactivity. However, a lower concentration of captopril (0.1 microM), which totally abolished the facilitatory effect of angiotensin I (0.1 microM) on the S-I outflow of radioactivity, failed to alter the facilitatory effect of isoproterenol. Angiotensin II (0.03 microM) enhanced markedly the S-I outflow of radioactivity and in the presence of the angiotensin II receptor blocking drug saralasin (0.1 microM) this facilitatory effect was reduced markedly. Saralasin did not alter the facilitatory effect of isoproterenol. These results suggest that stimulation of prejunctional beta-2 adrenoceptors on renal sympathetic nerve endings enhances norepinephrine release. This effect is independent of local angiotensin II production and does not involve activation of prejunctional angiotensin II receptors within the rat kidney. However, the inhibitory effect of a high concentration of captopril (5.0 microM) on beta-2 adrenoceptor-mediated facilitation of norepinephrine release remains to be clarified.
Rump
L C
LC
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Majewski
H
H
D000804:Angiotensin II / Q000096:biosynthesis* / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012504:Saralasin / Q000494:pharmacology
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000804:Angiotensin II; C026777:ICI 118551; D001262:Atenolol; D002216:Captopril; D012504:Saralasin; D007545:Isoproterenol; D009638:Norepinephrine