Angiotensin II contractions in coronary artery. Nature of receptors and calcium pools.
Pig coronary artery rings denuded of endothelium contract to the vasoactive hormone angiotensin II (Ang II). The nature of Ang II receptors and their Ca(2+)-pool utilization were examined for contraction of the artery rings and for increase in ultracellular [Ca2+] ([Ca2+]i) in smooth muscle cells cultured from them. Ang II contracted the arteries (EC50 = 7 +/- 4 nM) but with a lower maximal force (1.4 +/- 0.25 N/g tissue) than the contraction with 60 mM K+ (6.11 +/- 0.63 N/g tissue). In the cultured cells it caused a transient increase in [Ca2+]i with an EC50 value of 11 +/- 4 nM. The cells bound Ang II with a dissociation constant (Kd) of 7 +/- 2 nM. Based on the effects of the Ang II antagonists saralasin, DuPont 753, dithiothreitol and PD123319, the Ang II receptors responsible for contraction, increase in [Ca2+]i and Ang II binding to coronary artery smooth muscle were of type AT1. The contraction to Ang II was abolished by EGTA but not by nitrendipine. The sarcoplasmic Ca2+ pump inhibitors cyclopiazonic acid (10 microM CPA) and thapsigargin (1 microM) produced contractions of 4.35 +/- 0.73 and 2.07 +/- 0.54 N/g, respectively. Ang II contractions in the control arteries were nearly abolished upon pretreatment with CPA and thapsigargin. CPA and thapsigargin induced contractions were abolished by exposure to EGTA for 1 h but short exposure of the cells to EGTA only modulated the CPA or thapsigargin induced increase in [Ca2+]i; Ang II induced increase in [Ca2+]i was not inhibited by 1 microM nitrendipine but was reduced significantly by a 30-60 sec exposure to EGTA.(ABSTRACT TRUNCATED AT 250 WORDS)
Grover
A K
AK
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Fomin
V P
VP
Samson
S E
SE
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects*; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009568:Nitrendipine / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000378:metabolism; D013552:Swine
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D004533:Egtazic Acid; D009568:Nitrendipine