8-bromocyclic-gmp and Acute-Disease

It is unknown if cardiac ischemia has any deleterious effect on the contractile properties of nonischemic, peripheral vascular beds. Thus, the objective of the present study was to determine whether acute myocardial ischemia results in peripheral vascular dysfunction.. This study characterized force maintenance and the sensitivity to acetylcholine (ACh)-mediated smooth muscle (SM) relaxation of tertiary (3rd) mesenteric arteries from Sprague-Dawley rats following 30 min of myocardial ischemia. Both the phosphorylation of nonmuscle (NM) light chain (LC) and SM-LCs as well as the expression of myosin phosphatase targeting subunit 1 (MYPT1) were also determined. Our data demonstrate that acute myocardial ischemia resulted in vascular dysfunction of 3rd mesenteric vessels, characterized by decreases in force maintenance, ACh- and cGMP-mediated SM relaxation, the phosphorylation of NM-LCs and SM-LCs, and MYPT1 expression. Ischemia was also associated with an increase in protein polyubiquitination, suggesting that during ischemia MYPT1 is targeted for degradation or proteolysis.. Acute myocardial ischemia produces peripheral vascular dysfunction; the changes in LC phosphorylation and MYPT1 expression result in a decrease in both tone and the sensitivity to NO-mediated SM relaxation of the peripheral vasculature.

Topics: Acetylcholine; Acute Disease; Animals; Biomechanical Phenomena; Cyclic GMP; Enzyme Induction; Male; Membrane Potentials; Mesenteric Arteries; Muscle, Smooth, Vascular; Myocardial Infarction; Myosin Light Chains; Nitric Oxide; Phosphorylation; Potassium Chloride; Protein Phosphatase 1; Protein Processing, Post-Translational; Rats; Rats, Sprague-Dawley; Ubiquitination; Vasodilation

In the glycerol model of renal injury we describe an acute rise in systemic arterial pressure which is attended by a reduced vasodilatory response to acetylcholine in vivo; vasodilatory responses to verapamil, however, were not impaired. Neither arginine nor sodium nitroprusside diminished this rise in blood pressure; N(omega)-nitro-L-arginine methyl ester (L-NAME) elevated basal mean arterial pressure and markedly blunted the rise in mean arterial pressure following the administration of glycerol. Aortic rings from the glycerol-treated rat demonstrate an impaired vasodilatory response to acetylcholine, an effect not repaired by arginine; the vasodilatory responses to nitric oxide donors, sodium nitroprusside and SIN-1, were also impaired; 8-bromo-cGMP, at higher doses, evinced a vasodilatory response comparable to that observed in the control rings. This pattern of responses was not a nonspecific effect of aortic injury, since aortic rings treated with mercuric chloride, a potent oxidant, displayed an impaired vasodilatory response to acetylcholine but not to sodium nitroprusside. We conclude that in the glycerol model of heme protein-induced tissue injury, there is an acute elevation in mean arterial pressure attended by impaired endothelium-dependent vasodilatation in vitro and in vivo. We suggest that the acute scavenging of nitric oxide by heme proteins depletes the blood vessel wall of its endogenous vasodilator and permeation of heme proteins into the blood vessel wall may contribute to such sustained effects as observed in vitro.

Topics: Acetylcholine; Acute Disease; Animals; Blood Pressure; Cyclic GMP; Disease Models, Animal; Glycerol; Hemeproteins; Hypertension; Kidney; Male; Nitroprusside; Rats; Rats, Sprague-Dawley; Vasodilator Agents