Norepinephrine amplifies angiotensin II-induced vasoconstriction in rabbit femoral artery.
Several reports have focused on the ability of angiotensin II to amplify vascular contractile responses to norepinephrine, but none have determined whether norepinephrine enhances angiotensin II-induced vasoconstriction. Measuring isometric contraction in isolated rabbit femoral artery rings, we have found that the angiotensin II-induced contractile response was amplified in the presence of a threshold contraction to norepinephrine, as manifested by a 2.9-fold leftward shift of the midpoint of the concentration-response curve with no change in the maximal response. This amplification was attenuated markedly by nifedipine (0.1 microM), a calcium channel antagonist, implicating calcium channel activation in the amplification phenomenon. Precontracting the smooth muscle with a threshold concentration of angiotensin II had no enhancing effect on further angiotensin responses, indicating that the norepinephrine-induced amplification was due to a specific action of norepinephrine, rather than to a precontraction itself. In experiments in which the angiotensin II response was diminished by the presence of the noncompetitive angiotensin II antagonist [Sar1 Ala8]angiotensin II (0.3 microM), norepinephrine affected the angiotensin II response primarily by increasing the maximal response attainable. Prazosin (0.1 microM) both blocked the norepinephrine threshold contraction and abolished completely the amplification. However, when the norepinephrine concentration was increased until a threshold contraction was elicited in the presence of a fixed concentration of prazosin, amplification of the angiotensin II response was restored. These results indicate that norepinephrine exerts its amplifying effect on angiotensin II via activation of alpha-1 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Prins
B A
BA
Department of Pharmacology, University of California, Irvine.
Weber
M A
MA
Purdy
R E
RE
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D005263:Femoral Artery / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits; D012504:Saralasin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D000804:Angiotensin II; D012504:Saralasin; D009638:Norepinephrine