N omega-nitro-L-arginine selectively inhibits vasodilator responses to acetylcholine and bradykinin in cats

Abstract

The effects of N omega-nitro-L-arginine (nitroarginine), an inhibitor of endothelium-dependent relaxing factor (EDRF) production, on vascular tone and responses to vasodilator and vasoconstrictor agents were investigated in the hindquarters vascular bed of the cat. Under constant flow conditions, infusion of nitroarginine into the hindquarters vascular bed caused a significant increase in systemic arterial and hindquarters perfusion pressures. During infusion of nitroarginine, hindquarters vasodilator responses to acetylcholine and bradykinin were reduced significantly whereas vasodilator responses to isoproterenol, PGE1, nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate were not altered. Infusion of nitroarginine significantly enhanced vasoconstrictor responses to the thromboxane receptor agonist U 46619 and to phenylephrine. The results of these studies are consistent with the hypotheses that EDRF production may involve the formation of nitric oxide or a nitroso compound from L-arginine, and that EDRF production may play a role in the regulation of vascular tone and in the mediation of responses to the endothelium-dependent vasodilators, acetylcholine and bradykinin, in resistance vessels in the hindquarters. These data support the concept that EDRF is very likely an endogenous nitrovasodilator derived from L-arginine in the hindquarters vascular bed of the cat.

Competitive inhibition of nitric oxide synthase prevents the cortical hyperemia associated with peripheral nerve stimulation.

“…These findings are consistent with those of others who have demonstrated a role for basal endogenous nitric oxide in the control of vasomotor tone throughout the body (21,22). Finding an intermediate baseline cerebral blood flow in the experiments in which L-arginine was added to the CSF containing L-NAME also supports a role for nitric oxide in control of basal cerebral blood flow.…”

Regulation of baseline vascular resistance in the canine diaphragm by nitric oxide

“…In vivo studies have demonstrated increased baseline arterial pressure following systemic infusion of L-arginine analogues in rats (Gardiner et al, 1989), guinea-pigs (Aisaka et al, 1989), cats (Bellan et al, 1991) and dogs (Klabunde et al, 1990). Regionally, treatment with analogues of L-arginine have been found to increase vascular resistance in rabbit isolated hearts (Lamontagne et al, 1991), rabbit hindlimb (Mugge et al, 1991), dog hindlimb (White et al, 1993) and human forearm (Vallance et al, 1989).…”

“…Some studies have shown that the in vivo responses to endothelium-dependent agents are selectively inhibited by treatment with L-arginine analogues, while responses to endothelium-independent agents are not significantly decreased (Aisaka et al, 1989;Gold et al, 1989;Gardiner et al, 1989;Bellan et al, 1991;Kaley et al, 1992;White et al, 1993). Other studies, however, have shown either no decrease in responses to endothelium-dependent vasodilators (Mugge et al, 1991, Ross et al, 1991 or a non-selective inhibition of both endothelium-dependent and -independent vasodilatation (Thomas et al, 1989;Klabunde et al, 1990).…”

“…Other studies, however, have shown either no decrease in responses to endothelium-dependent vasodilators (Mugge et al, 1991, Ross et al, 1991 or a non-selective inhibition of both endothelium-dependent and -independent vasodilatation (Thomas et al, 1989;Klabunde et al, 1990). The degree to which L-arginine analogues are able to inhibit the vasodilatation induced by ACh has also been variable, prompting some authors to propose additional mechanisms of action for this vasodilator in their preparations (Gold et al, 1989;Bellan et al, 1991;Ross et al, 1991). The dose and duration of treatment have also been reported to alter the relative effect of L-arginine analogues on baseline vascular tone in comparison to their effects on the response to ACh (Bellan et al, 1991).…”

“…The degree to which L-arginine analogues are able to inhibit the vasodilatation induced by ACh has also been variable, prompting some authors to propose additional mechanisms of action for this vasodilator in their preparations (Gold et al, 1989;Bellan et al, 1991;Ross et al, 1991). The dose and duration of treatment have also been reported to alter the relative effect of L-arginine analogues on baseline vascular tone in comparison to their effects on the response to ACh (Bellan et al, 1991). Furthermore, the relative potencies of two of these agents L-NOARG and L-NMMA, in the in vivo canine femoral circulation has been shown to differ from that predicted from in vitro studies (Kirkeboen et al, 1992).…”