Angiotensin II amplification of alpha-adrenergic vasoconstriction: role of receptor reserve.
Angiotensin II (Ang II) is known to enhance the vasoconstrictor response to norepinephrine (NE). In the present study, this interaction was investigated using isolated rabbit femoral artery rings mounted in tissue baths for the measurement of isometric contraction. Exposure to 3 x 10(-10) M Ang II caused a contraction that was less than 5% of the maximal response to NE. In the presence of Ang II, the NE dose-response curve shifted to the left twofold and the maximal response was not changed. The calcium channel antagonist nifedipine, 1 x 10(-7) M, caused a modest inhibition of the response to NE in either the presence or absence of Ang II. In contrast, nifedipine abolished the leftward shift of the NE dose-response curve caused by Ang II. Femoral arteries were pretreated with benextramine to cause partial alpha-adrenoceptor inactivation. The maximal contractile response to NE in these tissues was between 20% and 40% of that in control vessels, indicating that alpha-adrenoceptor reserve had been eliminated. In benextramine-pretreated vessels, the presence of 3 x 10(-10) M Ang II caused a modest leftward shift of the NE dose-response curve but increased the maximal responses to all NE concentrations by 200% to 800%. Nifedipine caused a modest inhibition of the response to NE in the absence of Ang II. In contrast, the enhanced response to NE in the presence of Ang II was nearly abolished. These results support our conclusions that 1) Ang II enhances the vasoconstrictor response to alpha-adrenergic stimulation, 2) the magnitude of enhancement is greater under conditions of reduced alpha-receptor reserve, and 3) calcium channel activation plays a major role in the amplified response.
Purdy
R E
RE
Department of Pharmacology, University of California, Irvine 92717.
Weber
M A
MA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003538:Cystamine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005263:Femoral Artery / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D000804:Angiotensin II; D015016:Yohimbine; C029998:benextramine; D009543:Nifedipine; D003538:Cystamine; D009638:Norepinephrine; D011224:Prazosin