Angiotensin II amplifies arterial contractile response to norepinephrine without increasing Ca++ influx: role of protein kinase C.
We investigated whether the enhanced contractile response to norepinephrine caused by a subthreshold concentration of angiotensin II was associated with an increased 45Ca++ influx or net uptake. Rabbit facial artery segments were mounted isometrically to measure the 45Ca++ influx and net uptake in response to norepinephrine. The contractile response to norepinephrine (3 microM) in the presence of angiotensin II (0.1 nM) was 149.5 +/- 7.4% of control. This response amplification was not associated with changes in norepinephrine-induced 45Ca++ influx or net uptake. Angiotensin II also potentiated the contractile response to caffeine obtained in a Ca(++)-free buffer containing ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid (2 mM) to 148.0 +/- 4.8% of control. In both cases, the amplification was prevented by pretreatment with either staurosporine (10 nM) or calphostin C (100 nM), two inhibitors of protein kinase C. We conclude that angiotensin II potentiation of norepinephrine-induced vascular tone occurs in the absence of changes in stimulated Ca++ entry. This potentiation may be due to an increase in intracellular sensitivity to Ca++, possibly mediated by protein kinase C.
Henrion
D
D
Department of Pharmacology, University of Vermont, College of Medicine, Burlington.
Laher
I
I
Laporte
R
R
Bevan
J A
JA
D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004357:Drug Synergism; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009281:Naphthalenes; D009638:Norepinephrine / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011817:Rabbits; D019311:Staurosporine
D000470:Alkaloids; D009281:Naphthalenes; D011083:Polycyclic Compounds; D000804:Angiotensin II; D002110:Caffeine; D006632:Histamine; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C; D002118:Calcium; D009638:Norepinephrine