Angiotensin II contractions in coronary artery

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Abstract
Pig coronary artery rings denuded of endothelium contract to the vasoactive hormone angiotensin II (Ang II). The nature of Ang II receptors and their Ca2+-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 μM CPA) and thapsigargin (1 μM) 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 μM nitrendipine but was reduced significantly by a 30–60 sec exposure to EGTA. CPA and thapsigargin caused an increase in [Ca2+]i even after 30–200 sec exposure to EGTA. Ang II when added after CPA or thapsigargin did not cause a further increase in [Ca2+]i but when added before them it caused an increase in [Ca2+]i and reduced the increase caused by subsequent addition of CPA or thapsigargin. These data are consistent with the concept that Ang II utilizes an intracellular Ca2+-pool which is a small component of the CPA or thapsigargin sensitive Ca2+-pool.