We tested whether vasorelaxation of coronary arteries is altered after overnight (18-22 h) exposure to physiological levels of 17 beta-estradiol. Ring segments of left circumflex coronary artery from six female and six castrated male pigs were incubated in vials of sterile Dulbecco's modified Eagle's medium with 1 nM 17 beta-estradiol, 1 nM 17 beta-estradiol + 10 nM tamoxifen, 1 nM 17 alpha-estradiol, or estrogen vehicle (ethanol) under normoxic conditions in an O2-CO2 incubator at 37 degrees C for 18-22 h. Coronary rings, with and without endothelium, were then suspended in vessel baths for measurement of isometric force. Vasorelaxation responses to the calcium ionophore A-23187, ADP, and nitroglycerin were examined in the rings after prostaglandin synthesis blockade and precontraction with U-46619. Sensitivity to A-23187 (-log M concentration required for 50% of maximal relaxation) was significantly enhanced in coronary rings with endothelium from females and castrated males when rings were incubated with 17 beta-estradiol but not when they were incubated with 17 alpha-estradiol or 17 beta-estradiol+tamoxifen. Acute (2h) exposure of coronary arteries to 1 nM 17 beta-estradiol did not alter responses to A-23187. 17 beta-Estradiol (1 nM) was not itself directly vasoactive in coronary arteries with or without prior incubation with the steroid. Vasorelaxation of rings with and without endothelium to ADP and nitroglycerin was not significantly different among the treatment groups. Relaxation to A-23187, but not ADP, was abolished by removal of the endothelium or exposure to 100 microM NO2-L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
We tested the hypothesis as to whether elevated arterial pressure in hypertension alters cGMP, or cAMP, mediated vasorelaxation. Relaxation to nitroglycerin and isoproterenol was determined in isolated aortic rings from one-kidney, one clip hypertensive (1K1C), coarctation hypertensive (CH) and normotensive control (C) rats. Thoracic aortas from 1K1C and CH rats, as well as abdominal aortas from 1K1C rats, but not abdominal aortas from CH rats were exposed chronically (4-6 weeks) to elevated arterial pressure. Sensitivity of rings with and without endothelium to nitroglycerin was suppressed significantly only in vessels exposed chronically to high arterial pressure. Impaired sensitivity to nitroglycerin in abdominal rings from 1K1C rats could not be abolished by exposure to 100 uM L-arginine, the substrate for production of NO by endothelial nitric oxide synthase, or 100 uM L-cysteine, the source of thiol groups required for the production of nitric oxide from nitroglycerin. Maximum relaxation to isoproterenol was impaired significantly in thoracic and abdominal rings, with and without endothelium, from 1K1C and CH rats. Relaxation to 8-bromo-cGMP and dibutyryl cAMP was similar in abdominal rings from all groups. We conclude that impaired vasorelaxation to nitroglycerin and isoproterenol in hypertension involves mechanisms prior to activation of vascular smooth muscle cGMP-dependent and cAMP-dependent protein kinase, respectively. Impaired cGMP, but not cAMP, mediated relaxation of aortas appears to result from their exposure to high arterial pressure per se. This effect does not appear to involve the vascular endothelium or vascular sources of thiols, but rather may reflect an effect of high arterial pressure to impair the ability of the artery to respond to nitric oxide derived from nitroglycerin.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.