Role of nitric oxide and cyclic GMP as mediators of endothelium-independent neurogenic relaxation in bovine mesenteric artery.

Abstract

Electrical field stimulation (EFS) of phenylephrine-contracted bovine mesenteric arteries pretreated with guanethidine elicited a relaxation that amounted to roughly 40%. This relaxation was sensitive to tetrodotoxin pretreatment, suggesting a neurogenic origin. The EFS-induced relaxation was correlated to an increase in cGMP level, from 14.2 +/- 2.5 pmol/g wet wt in nonstimulated arteries to 31.6 +/- 3.4 pmol/g wet wt after 1 minute of EFS. cAMP values were not affected by EFS. Methylene blue (5 microM) and the compound LY 83583 (10 microM), inhibitors of soluble guanylate cyclase, inhibited the EFS-induced relaxation by 60% and 50%, respectively. Zaprinast (1 microM), a selective inhibitor of cGMP degradation, significantly (p = 0.005) potentiated the EFS-induced relaxation. The relaxation induced by EFS in bovine mesenteric arteries exhibits characteristics similar to the relaxations evoked by organic nitroesters and endothelium-dependent vasodilators, both of which are suggested to be mediated by cGMP and probably with nitric oxide as the common activator of the cGMP system. The possible involvement of nitric oxide as a mediator of EFS-induced relaxations was investigated with the use of known modulators of endogenous nitric oxide production. Preincubation of the arteries with 1 mM arginine or 1 mM N-alpha-benzoyl-L-arginine, both reported to potentiate endogenous nitric oxide production, or 5 mM L-canavanine, 0.25 mM NG-monomethyl-L-arginine, or 0.1 mM NG-nitro-L-arginine, alleged inhibitors of endogenous nitric oxide production, were without effect on the relaxation induced by EFS. However, pyrogallol, a generator of superoxide anions, was a potent inhibitor of relaxations induced by EFS in bovine mesenteric arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of systemic and pulmonary blood pressure by nitric oxide formed through neuronal nitric oxide synthase

“…Furthermore, there is some reported evidence indicating that peripheral arteries, such as mesenteric [23][24][25], renal [26], pulmonary [27], ocular [28,29], lingual [30], and cutaneous arteries [31], in a variety of mammals including monkeys are innervated by nitrergic nerves that contribute to counteracting vasoconstrictor sympathetic nerve functions. Transmural electrical stimulation or nicotine has been used to stimulate perivascular nerves to liberate neurotransmitters, such as norepinephrine and nitric oxide, in vitro and in vivo.…”

The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

“…In dog (Toda et al, 1991b), monkey (Toda and Okamura, 1992b), cow (Ahlner et al, 1991;Leckstrom et al, 1993), and guinea pig mesenteric arteries (Gyoda et al, 1995) partially contracted with vasoconstrictors, electrical nerve stimulation or nicotine caused a contraction that was reversed to a relaxation by treatment with ␣-adrenoceptor antagonists or adrenergic neuron blockers. The relaxation was independent of the endothelium and was abolished by the L-enantiomers of NOS inhibitors, and L-arginine restored the response.…”

“…The relaxation was independent of the endothelium and was abolished by the L-enantiomers of NOS inhibitors, and L-arginine restored the response. Neurogenic relaxation was inhibited by methylene blue but was potentiated by inhibitors of cyclic GMP phosphodiesterase (Ahlner et al, 1991). Tissue cyclic GMP was increased by nerve stimulation (Toda et al, 1991b;Toda and Okamura, 1992b).…”

Modulation of blood flow and tissue perfusion by endothelium‐derived relaxing factor

“…Non-cholinergic, non-adrenergic (NANC) nerves themselves synthesize NO, thereby regulating smooth muscle tone and motility in the gastrointestinal and urinary tracts (Desai, Sessa & Vane, 1991;Burnett, Lowenstein, Bredt, Chang & Snyder, 1992). Adventitial NANC nerves similarly relax pelvic, cerebral and mesenteric arteries by releasing NO, thereby mediating penile erection, in which neuronal synthesis of NO dominates over endothelial (Toda & Okamura, 1990;Ahlner, Ljusegren, Grundstrom & Axelsson, 1991;Burnett et al 1992). It is also possible that NANC-derived NO modulates gastric mucosal flow (Whittle, 1993).…”