New 2-Aminothiazoline derivatives lower blood pressure of spontaneously hypertensive rats (SHR) via I-imidazoline and alpha-2 adrenergic receptors activation.

2-Aminothiazolines share an isosteric relationship with imidazolines and oxazolines with antihypertensive activity mainly mediated by the imidazoline I-receptor. In the present work, we have prepared five aminothiazolines, following a previously described synthetic pathway. Aminothiazolines derived from dicyclopropylmethylamine (ATZ1) and cyclohexylamine (3) are unprecedented in the literature.

A pivotal role for enhanced brainstem Orexin receptor 1 signaling in the central cannabinoid receptor 1-mediated pressor response in conscious rats.

Orexin receptor 1 (OX1R) signaling is implicated in cannabinoid receptor 1 (CB1R) modulation of feeding. Further, our studies established the dependence of the central CB1R-mediated pressor response on neuronal nitric oxide synthase (nNOS) and extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation in the RVLM. Here, we tested the novel hypothesis that brainstem orexin-A/OX1R signaling plays a pivotal role in the central CB1R-mediated pressor response.

Cannabinoid receptor 1 signaling in cardiovascular regulating nuclei in the brainstem: A review.

Cannabinoids elicit complex hemodynamic responses in experimental animals that involve both peripheral and central sites. Centrally administered cannabinoids have been shown to predominantly cause pressor response. However, very little is known about the mechanism of the cannabinoid receptor 1 (CB1R)-centrally evoked pressor response.

Oxidative stress and autonomic dysregulation contribute to the acute time-dependent myocardial depressant effect of ethanol in conscious female rats.

Background: The molecular mechanisms of the acute hypotensive and indirectly assessed cardiac depressant effect of ethanol (EtOH)-evoked myocardial depression and hypotension in female rats are not known. We tested the hypothesis that a time-dependent myocardial depression caused by EtOH is initiated by its direct and indirect (cardiac vagal dominance) effects and is exacerbated by gradual development of oxidative stress.

Methods: In conscious female rats, we directly measured left ventricular developed pressure (LVDP), the maximal rise of ventricular pressure over time (dP/dtmax ), blood pressure (BP), heart rate (HR), and sympathovagal activity following intragastric EtOH (1 g/kg) or water over 90 minutes.

Activation of renal haeme oxygenase-1 alleviates gentamicin-induced acute nephrotoxicity in rats.

Objectives: This study aimed to investigate whether activation of haeme oxygenase (HO)-1 enzyme by haemin would have beneficial effects on the functional and histological outcome against gentamicin-induced renal damage in rats and sought to elucidate the underlying mechanisms of the therapeutic action.

Methods: Nephrotoxicity was induced by injection of gentamicin (80 mg/kg, i.p.

Enhancement of rostral ventrolateral medulla neuronal nitric-oxide synthase-nitric-oxide signaling mediates the central cannabinoid receptor 1-evoked pressor response in conscious rats.

Our recent studies implicated brainstem GABAergic signaling in the central cannabinoid receptor 1 (CB(1)R)-mediated pressor response in conscious rats. Given the well established link between neuronal nitric-oxide synthase (nNOS)/nitric oxide (NO) signaling and GABAergic transmission in brainstem cardiovascular regulating areas, we elucidated the role of nNOS-generated NO in the central CB(1)R-elicited pressor response. Compared with vehicle, intracisternal (i.

Differential modulation of brainstem phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase 1/2 signaling underlies WIN55,212-2 centrally mediated pressor response in conscious rats.

Our recent study demonstrated that central cannabinoid receptor 1 (CB₁R) activation caused dose-related pressor response in conscious rats, and reported studies implicated the brainstem phosphatidylinositol 3-kinase (PI3K)/Akt-extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in blood pressure control. Therefore, in this study, we tested the hypothesis that the modulation of brainstem PI3K/Akt-ERK1/2 signaling plays a critical role in the central CB(1)R-mediated pressor response. In conscious freely moving rats, the pressor response elicited by intracisternal (i.

Role of brainstem GABAergic signaling in central cannabinoid receptor evoked sympathoexcitation and pressor responses in conscious rats.

The mechanisms implicated in the sympathoexcitation and pressor responses elicited by central CB₁R activation are not fully understood. Further, the few reported mechanistic studies on this endeavor were conducted in anesthetized rats. Therefore, it was important to identify the dose-related cardiovascular responses elicited by central administration of the cannabinoid receptor (CB₁R) agonist WIN55,212-2 in conscious rats.