Inhibition of salt appetite in sodium-depleted rats by carvacrol: Involvement of noradrenergic and serotonergic pathways.

Carvacrol, a monoterpene phenol present in the essential oil of oregano, possesses several biological properties, such as antioxidant, anti-inflammatory, anxiolytic, anticonvulsive and antinociceptive. In vitro studies have shown that carvacrol inhibits serotonin, noradrenaline and dopamine transporters and the enzymes monoamine oxidase-A and B. Different brain functions are controlled by monoamines, including cardiovascular control, thirst and sodium appetite. In the present study we investigated the effects of intracerebroventricular (i.c.v.) injection of carvacrol on sodium appetite, and the participation of brain serotonergic and noradrenergic pathways on carvacrol effects. Neuronal activation in homeostasis-related brain areas induced by i.c.v. injection of carvacrol was also evaluated. Carvacrol dose-dependently inhibited hypertonic saline intake (1.5%) in sodium-depleted rats, and this antinatriorexigenic effect was reduced by brain serotonergic depletion and by alpha-adrenergic blockade. Furthermore, i.c.v. injections of carvacrol significantly increased the neuronal activation in brain areas involved in the control of salt appetite, such as MnPO, OVLT, PVN, SON, CeA and MeA. Taken together, our data show that carvacrol presents antinatriorexigenic activity through serotonin and noradrenaline pathways within brain circuits involved in the modulation of the body fluid homeostasis.

Hypertensive response to stress: the role of histaminergic H1 and H2 receptors in the medial amygdala.

Different brain areas seem to be involved in the cardiovascular responses to stress. The medial amygdala (MeA) has been shown to participate in cardiovascular control, and acute stress activates the MeA to a greater extent than any of the other amygdaloid structures. It has been demonstrated that the brain histaminergic system may be involved in behavioral, autonomic and neuroendocrine responses to stressful situations. The aim of the present study was to investigate the role of the histaminergic receptors H1 and H2 in cardiovascular responses to acute restraint stress. Wistar rats (280-320g) received bilateral injections of cimetidine, mepyramine or saline into the MeA and were submitted to 45min of restraint stress. Mepyramine microinjections at doses of 200, 100 and 50nmol promoted a dose-dependent blockade of the hypertensive response induced by the restraint stress. Cimetidine (200 and 100nmol) promoted a partial blockade of the hypertensive response to stress only at the highest dose administered. Neither drugs altered the typical stress-evoked tachycardiac responses. Furthermore, mepyramine and cimetidine were unable to modify the mean arterial pressure or heart rate of freely moving rats under basal conditions (non-stressed rats). The data suggest that in the MeA the histaminergic H1 receptors appear to be more important than H2 receptors in the hypertensive response to stress. Furthermore, there appears to be no histaminergic tonus in the MeA controlling blood pressure during non-stress conditions.

Effect of the activation of central 5-HT2C receptors by the 5-HT2C agonist mCPP on blood pressure and heart rate in rats.

In the present study we investigated the role of central 5-HT2C receptors in the control of blood pressure and heart rate in non-stressed and stressed, adult, male, Wistar rats. Third ventricle injections of the 5-HT2C agonist mCPP elicited a significant increase in blood pressure in non-stressed animals. The initial period of this hypertensive response (10-30 min after mCPP administration) was accompanied by baroreflex-mediated bradycardia, while after this period the coexistence of hypertension and tachycardia was observed. These cardiovascular effects promoted by the central administration of mCPP were blocked by pretreatment with the 5-HT2C antagonist, SDZ SER 082. The administration of SDZ SER 082 alone induced no significant changes in blood pressure or heart rate. The pharmacological stimulation of central 5-HT2C receptors by mCPP did not change the hypertensive or tachycardic responses induced by restraint stress. Conversely, the blockade of central 5-HT2C receptors by SDZ SER 082 blunted stress-induced hypertension without modifying stress-induced tachycardia. It is concluded that the activation of central 5-HT2C receptors induces hypertension in non-stressed rats and that the normal function of these receptors is essential for the rise in blood pressure that occurs in the course of restraint stress.

Role of central 5-HT3 receptors in the control of blood pressure in stressed and non-stressed rats.

The aim of the present study was to investigate the participation of central 5-HT(3) receptors in the control of blood pressure and heart rate (HR) of non-stressed and stressed rats. The pharmacological stimulation of brain 5-HT(3) receptors by third ventricle injections of the selective 5-HT(3) receptor agonist m-CPBG induced a significant decrease in blood pressure in non-stressed rats and impaired the hypertensive response induced by restraint stress. The blockade of brain 5-HT(3) receptors by the central administration of the selective 5-HT(3) antagonist ondansetron elicited a significant increase in blood pressure in non-stressed rats. Conversely, the hypertensive response induced by restraint stress was not affected by central administration of ondansetron. Additionally, baroreflex-mediated bradycardia during phenylephrine-induced hypertensive response was preserved in non-stressed animals receiving third ventricle injections of m-CPBG, while the baroreflex-mediated tachycardia that occurs during the hypotensive response induced by the administration of sodium nitroprusside was impaired. It is concluded that the serotoninergic component represented by the brain 5-HT(3) receptors exerts a tonic inhibitory influence on the central control of blood pressure in non-stressed rats, probably by a sympathoinhibitory-related mechanism. On the other hand, during stress, this central 5-HT(3)-dependent inhibitory drive is overwhelmed by the different neurochemical systems that harmonically trigger and sustain the hypertensive response.

Central administration of zinc reduces salt intake in rats.

The aim of the present study was to investigate the effect of third ventricle injections of zinc on salt intake in rats in the three different experimental models where sodium appetite is increased: fluid deprivation, central angiotensinergic stimulation and sodium depletion. Adult Wistar male rats received third ventricle injections of Zn(Ac)2 in three different doses (0.03, 0.3 and 3.0 nmol/rat). Central angiotensinergic stimulation was achieved by third ventricle injections of angiotensin II in the dose of 25 ng/rat 30 min before central zinc administration. As expected, fluid deprivation, central angiotensinergic stimulation and sodium depletion significantly increased sodium appetite. Water intake was also enhanced after fluid deprivation and central angiotensinergic stimulation. After sodium depletion, no increase in water intake was observed. Third ventricle injections of zinc inhibited salt intake in all three experimental models studied. Water intake was also inhibited by central zinc administration after fluid deprivation and central angiotensinergic stimulation. Conversely, third ventricle injections of zinc were unable to modify food intake or body temperature. It is suggested that zinc, acting on central structures related to the control of body fluid homeostasis, inhibits the drive for salt intake that is normally observed during fluid deprivation, central angiotensinergic stimulation and sodium depletion.