Effects of the chronic in vivo administration of L‐NAME on the contractile responses of the rat perfused mesenteric bed

Abstract

The effects of the chronic in vivo inhibition of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine methyl ester (L-NAME) on vascular contractility were studied in the rat perfused mesenteric bed. The chronic treatment with L-NAME during 4 weeks induced a rise in systolic blood pressure (basal: 115.1 +/- 6.5 mmHg; chronic L-NAME treatment: 171.7 +/- 7.7 mmHg, n = 16, P < 0.05). After the chronic NOS inhibition, the potentiation of the maximal vasoconstrictor responses to noradrenaline, phenylephrine and KCl was to the same extent as that observed after the in vitro exposure to 100 microM L-NAME. No further potentiation of the contractile responses was achieved when the mesenteric beds isolated from L-NAME treated rats were incubated in vitro with 100 microM L-NAME. The endothelium removal but not the inhibition of prostanoid synthesis with either 10 microM indomethacin or 10 microM 17-octadecynoic acid potentiated the contractions to noradrenaline and to KCl both under control conditions as well as after the chronic in vivo administration of L-NAME. These observations taken together suggest that after chronic L-NAME maximum inhibition of nitric oxide synthase was achieved and no compensatory mechanisms able to counterbalance the increase in contractile responses were developed. Further studies are necessary to elucidate the nature of the factors, other than nitric oxide, that contribute to the potentiation of contractile responses observed when the endothelium is removed after L-NAME treatment.

Attenuated Agonist Evoked Vasoconstrictor Responses in the Perfused Mesenteric Vascular Bed of Streptozotocin Diabetic Rats

“…Indeed, in our hands, indomethacin has never been shown to increase (or decrease) the responses to vasoconstrictor agonists in the perfused MVB (8,19). This inability has also been demonstrated by others, using the same vascular bed preparation (20)(21)(22).…”

Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension

“…L-NAME-induced hypertension is a model consisting of the systemic inhibition of NO synthesis by orally or intravenously administered L-NAME. This model displays cardiovascular (298,445,595,661) and renal (61,178,469,662,685) alterations, as well as alteration to the nervous system (221,606). Renal NO regulates GFR (372,396), renal blood flow (372,740), medullary blood flow (112,435), pressure natriuresis (418,604), transport processes (186,543), and renin release (39,675).…”

Phytoestrogens Enhance the Vascular Actions of the Endocannabinoid Anandamide in Mesenteric Beds of Female Rats

“…Taking into account that the anandamide effect is already greater in female mesenteries compared to males [16], the enhancing effect of the phytoestrogens shown here in female rats adds to the overall sex differentiation in this model. The tissue was selected because it represents a group of resistance vessels that greatly contributes to the maintenance of the total peripheral vascular resistance [17, 18]. Precontractions to NA were used to resemble the effects of the adrenergic hyperactivity in vascular tissues that usually precedes the onset of primary hypertension [12].…”

“…Up to nine consecutive, 20 min apart bolus injections of noradrenaline (NA) were performed in one preparation because the short contractile responses induced by this drug are highly reproducible. On the contrary, the sustained contractions that are obtained whenever the agonists are added to the perfusate are difficult to reproduce in the same preparation [17]. …”