Endothelium-dependent modulation of cGMP levels and intrinsic smooth muscle tone in isolated bovine intrapulmonary artery and vein.

Abstract

The role of the endothelium in modulating cyclic nucleotide levels and intrinsic smooth muscle tone was studied in isolated rings of bovine intrapulmonary artery and vein. Cyclic 3',5'-guanosine monophosphate (cGMP) levels were threefold to fourfold higher in unrubbed artery and vein than in vessels that had been denuded of endothelium. Cyclic 3',5'-adenosine monophosphate (cAMP) levels were twofold higher in unrubbed than in endothelium-denuded artery, but no differences were observed in veins. Methylene blue, an inhibitor of guanylate cyclase, decreased cGMP but not cAMP levels, and this was accompanied by increases in smooth muscle tone. M&B 22,948, an inhibitor of cGMP-phosphodiesterase, increased cGMP but not cAMP levels, and this was accompanied by decreases in smooth muscle tone. Unrubbed vessels were more sensitive than endothelium-denuded vessels to the actions of both methylene blue and M&B 22,948, and this may be attributed to endothelium-dependent increases in cGMP turnover. Moreover, unrubbed vessels were more sensitive than endothelium-denuded vessels to contractile responses to phenylephrine and potassium, and these responses were potentiated by methylene blue and attenuated by M&B 22,948. Although indomethacin lowered cAMP levels in unrubbed artery, no changes in tone or contractile responsiveness were observed. A consistent observation was that the smaller branches of unrubbed but not endothelium-denuded intrapulmonary artery and vein had higher levels of cGMP but not cAMP, were sensitive to endothelium-dependent vasodilators, were more sensitive to methylene blue, and would not maintain a steady level of submaximal tone to phenylephrine when compared with larger branches from a common vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of nitric oxide and guanosine 3′,5′‐cyclic monophosphate in mediating nonadrenergic, noncholinergic relaxation in guinea‐pig pulmonary arteries

“…The ability of methylene blue to elevate further U44069-generated tension indicates that there is an intrinsic NOindependent generation of cyclic GMP, which may also modulate the intrinsic smooth tone. Similar findings have been made in bovine pulmonary arteries (Ignarro et al, 1987).…”

Nitric oxide as a cellular antioxidant: A little goes a long way

“…It is involved in signalling in vasodilatation [1,2,3,4] and neurotransmission [5], a toxin in the destruction of pathogens [6,7], and a precursor to oxidizing and nitrating species [8,9]. However, its diverse chemistry and its biologic activity sometimes are seemingly contradictory.…”

“…Nowhere is this contradiction more evident than in oxidative stress. Nitric oxide has been proposed to act as a pro-oxidant at high concentrations [10] or when it reacts with superoxide (O 2 •− ) forming the highly reactive peroxynitrite (ONOO − ) [11,12,13]. On the other hand, NO • can also inhibit oxidation; NO • can terminate chain reactions during lipid peroxidation, as observed in model lipid systems [14,15], low density lipoprotein oxidation [16,17,18,19] and in cells [20,21].…”

Cyclic GMP‐independent relaxation and hyperpolarization with acetylcholine in guinea‐pig coronary artery

“…NO diffuses to the adjacent vascular smooth muscle cells where it stimulates soluble guanylyl cyclase activity leading to increased cyclic GMP levels (Ignarro, 1989;Moncada et al, 1991). Both the relaxation and enhanced guanylyl cyclase activity produced by ACh can be mimicked by addition of authentic NO (Gruetter et al, 1981;Ignarro et al, 1987).…”