These data indicate that central nitric oxide arising from the inducible nitric oxide synthase pathway plays an important inhibitory role in vasopressin release during experimental septic shock and may be responsible for the hypotension occurring in this vasodilatory shock.

Our hypothesis is that oxytocin (OT) causes natriuresis by activation of renal NO synthase that releases NO followed by cGMP that mediates the natriuresis. To test this hypothesis, an inhibitor of NO synthase, L-nitroarginine methyl ester (NAME), was injected into male rats. Blockade of NO release by NAME had no effect on natriuresis induced by atrial natriuretic peptide (ANP). This natriuresis presumably is caused by cGMP because ANP also activates guanylyl cyclase, which synthesizes cGMP from GTP. The 18-fold increase in sodium (Na ؉ ) excretion induced by OT (1 g) was accompanied by an increase in urinary cGMP and preceded by 20 min a 20-fold increase in NO 3 ؊ excretion. NAME almost completely inhibited OT-induced natriuresis and increased NO 3 ؊ excretion; however, when the dose of OT was increased 10-fold, a dose that markedly increases plasma ANP concentrations, NAME only partly inhibited the natriuresis. We conclude that the natriuretic action of OT is caused by a dual action: generation of NO leading to increased cGMP and at higher doses release of ANP that also releases cGMP. OT-induced natriuresis is caused mainly by decreased tubular Na ؉ reabsorption mediated by cGMP. In contrast to ANP that releases cGMP in the renal vessels and the tubules, OT acts on its receptors on NOergic cells demonstrated in the macula densa and proximal tubules to release cGMP that closes Na ؉ channels. Both ANP-and OT-induced kaliuresis also appear to be mediated by cGMP. We conclude that cGMP mediates natriuresis and kaliuresis induced by both ANP and OT.Atrial natriuretic peptide (ANP) and oxytocin (OT) are natriuretic hormones that play a fundamental role in the regulation of extracellular fluid volume. The natriuretic action of ANP has been explained by its combination with ANP A receptors on kidney cells that convert GTP into cGMP by activating particulate guanylate cyclase (GC). This form of GC (GC A ) is the cell surface receptor for ANP (1). In contrast, OT is a potent natriuretic peptide and OT receptors occur in the kidney, but the mechanism of OT-induced natriuresis is not clearly understood (2-7).The release of ANP that follows blood volume expansion is partly mediated by renal and arterial baroreceptor input to the brain stem that stimulates OT release from the neurohypophysis. Circulating OT binds to its receptors in the right atrium and stimulates ANP release from atrial myocytes (8,9). Because the injection of OT evoked concomitant release of ANP and natriuresis (10), the natriuretic action of OT might be mediated by the release of ANP that activates renal GC A receptors localized in glomeruli, their afferent and efferent arterioles, and the tubules (11). ANP selectively dilates preglomerular vessels and constricts efferent arterioles, thereby increasing the filtration fraction (FF). If the glomerular filtration rate (GFR) and tubular reabsorption of sodium (Na ϩ ) remain constant, this increase in FF would provide an increased filtered load (FL) of Na ϩ , resulting in natriuresis (12).In addition t...

Hypothermia is a response to hypoxia that occurs in organisms ranging from protozoans to mammals, but very little is known about the mechanisms involved. Recently, the NO pathway has been suggested to be involved in thermoregulation. In the present study, we assessed the participation of nitric oxide in hypoxia-induced hypothermia by means of NO synthase inhibition using NG-nitro-L-arginine methyl ester (L-NAME). The rectal temperature of awake, unrestrained rats was measured before and after hypoxia or L-NAME injection or both treatments together. Control animals received saline injections of the same volume. We observed a significant (P < 0.05) reduction in body temperature of 1.32 +/- 0.36 degrees C after hypoxia (7% inspired O2) and of 0.96 +/- 0.42 degree C after L-NAME (30 mg/kg body wt) injected intravenously. When the two treatments were combined, no significant difference in body temperature was observed. To assess the role of central thermo-regulatory mechanisms, a smaller dose of L-NAME (1 mg/kg) was injected into the third cerebral ventricle or intravenously. Intracerebroventricular injection of L-NAME caused an increase in body temperature, but when L-NAME was combined with hypoxia (7% inspired O2) no change in body temperature was observed. Intravenous injection of 1 mg/kg L-NAME had no effect. The data indicate that NO plays a major role in hypoxia-induced hypothermia at central rather than peripheral sites.

No abstract

No abstract

No abstract

No abstract

BackgroundObesity leads to a chronic inflammatory state, endothelial dysfunction and hypertension.ObjectiveTo establish the time-course of events regarding inflammatory markers, endothelial dysfunction, systolic blood pressure (SBP) in obesity in only one experimental model.MethodsWe fed male Wistar rats (eight-week age) with a standard diet (Control - CT, n = 35), or palatable high-fat diet (HFD, n = 35) for 24 weeks. Every six weeks, 7 animals from each group were randomly selected for euthanasia. SBP and serum levels of interleukin-6, tumor necrosis factor-α, C-reactive protein, adiponectin and nitric oxide were determined. Endothelial and vascular smooth muscle functions were determined in dissected aorta and lipid peroxidation was measured. Statistical significance was set at p < 0.05.ResultsLevels of pro-inflammatory cytokines began to increase after six weeks of a high-fat diet, while those of the anti-inflammatory cytokine adiponectin decreased. Interestingly, the endothelial function and serum nitric oxide began to decrease after six weeks in HFD group. The SBP and lipid peroxidation began to increase at 12 weeks in HFD group. In addition, we showed that total visceral fat mass was negatively correlated with endothelial function and positively correlated with SBP.ConclusionOur results show the time-course of deleterious effects and their correlation with obesity.