ABSTRACT
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.
Subject(s)
Blood Pressure/physiology , Cyclic AMP/physiology , Cyclic GMP/physiology , Hypertension, Renovascular/physiopathology , Vasodilation/physiology , Animals , Aorta, Abdominal/drug effects , Aorta, Abdominal/physiopathology , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiopathology , Bucladesine/pharmacology , Cyclic GMP/analogs & derivatives , Cyclic GMP/pharmacology , In Vitro Techniques , Isoproterenol/pharmacology , Nitric Oxide/pharmacology , Nitric Oxide/physiology , Nitroglycerin/pharmacology , Rats , Rats, Sprague-Dawley , Vasodilation/drug effectsABSTRACT
A large collection of potentially valuable materials compiled by the late Dr Derek Denny-Brown is described. This consists of 2,200 films of monkeys with central nervous system lesions, associated behavior and neuropathological descriptions, and histological slides. There are also 500 films of patients with a wide assortment of diseases, including some not currently seen, like postencephalitic parkinsonism. This description will enable contemporary researchers to utilize this collection in their research and teaching programs.
