Pertussis toxin attenuates angiotensin II-induced vasoconstriction and inhibition of renin release.
Angiotensin II can elicit cellular responses by 2 different receptor-dependent mechanisms: increase in intracellular calcium or inhibition of adenylate cyclase activity. The well-known inhibition of renin release from granulated cells of the kidney is thought to be mediated by an increase in intracellular calcium. However, the participation of the other possible pathway, i.e. inhibition of adenylate cyclase, has not been excluded. We studied this question by using the toxin from Bordetella pertussis, which inactivates the inhibitory coupling units Ni and thus permits to identify hormonal actions mediated through inhibition of adenylate cyclase. In isolated perfused kidneys from rats pretreated with pertussis toxin (2 micrograms/100 g i.v., single injection) the inhibition of renin release by angiotensin II (10(-11) to 10(-8) M) was significantly attenuated. In parallel, the vasoconstrictor response to angiotensin II was also diminished in these rat kidneys. The effect of pertussis toxin was apparent 3, 5 and 10 days after treatment, with a maximal effect at the fifth day. These data suggest that angiotensin II may exert the inhibitory effect on renin release in part through inhibition of adenylate cyclase in granulated cells of the kidney.
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D037342:Pertussis Toxin; D010648:Phenylacetates / Q000494:pharmacology; D051381:Rats; D012083:Renin / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D006146:Guanidines; D010648:Phenylacetates; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D016316:Guanfacine; D037342:Pertussis Toxin; D012083:Renin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases