The new nitric oxide donor cyclohexane nitrate induces vasorelaxation, hypotension, and antihypertensive effects via NO/cGMP/PKG pathway

We investigated the cardiovascular effects induced by the nitric oxide donor Cyclohexane Nitrate (HEX). Vasodilatation, NO release and the effects of acute or sub-chronic treatment with HEX on cardiovascular parameters were evaluated. HEX induced endothelium-independent vasodilatation (Maximum effect- [efficacy, ME] = 100.4±4.1%; potency [pD2] = 5.1±0.1). Relaxation was attenuated by scavenging nitric oxide (ME = 44.9±9.4% vs. 100.4±4.1%) or by inhibiting the soluble guanylyl cyclase (ME = 38.5±9.7% vs. 100.4±4.1%). In addition, pD2 was decreased after non-selective blockade of K+ channels (pD2 = 3.6±0.1 vs. 5.1±0.1) or by inhibiting KATP channels (pD2 = 4.3±0.1 vs. 5.1±0.1). HEX increased NO levels in mesenteric arteries (33.2±2.3 au vs. 10.7±0.2 au, p<0.0001). Intravenous acute administration of HEX (1-20 mg/kg) induced hypotension and bradycardia in normotensive and hypertensive rats. Furthermore, starting at six weeks after the induction of 2K1C hypertension, oral treatment with the HEX (10 mg/Kg/day) for seven days reduced blood pressure in hypertensive animals (134±6 vs 170±4 mmHg, respectively). Our data demonstrate that HEX is a NO donor able to produce vasodilatation via NO/cGMP/PKG pathway and activation of the ATP-sensitive K+ channels. Furthermore, HEX acutely reduces blood pressure and heart rate as well as produces antihypertensive effect in renovascular hypertensive rats

A Newly Isolated Carboxymethyl-Glucan (CM-G) Restores Depressed Baroreflex Sensitivity in Renovascular Hypertensive Rats

This study was designed to investigate the effects of a newly synthesized carboxymethyl-glucan (CM-G) on blood pressure (BP), baroreflex sensitivity (BRS) and sympathetic vascular modulation in renovascular hypertensive rats. Male Wistar rats were divided into four groups: Sham (n = 10); 2K1C (subjected to renal artery clipping to induce renovascular hypertension, n = 10); Sham + CM-G (treated with CM-G, n = 7) and 2K1C + CM-G (treated with CM-G, n = 7). The daily treatment with CM-G (40 mg/kg) was performed for 2 weeks. Blood pressure, heart rate (HR), systolic BP variability, baroreflex sensitivity (BRS) and sympathetic vascular tone were evaluated. After six weeks of renal artery clipping, 2K1C rats exhibited arterial hypertension (171 ± 11 vs. 118 ± 4 mmHg, p &lt; 0.05), impaired BRS (-1.30 ± 0.10 vs. -2.59 ± 0.17 bpm.mmHg-1, p &lt; 0.05) and enhanced sympathetic activity as shown by the hexamethonium test (-60 ± 5 vs. -33 ± 2 ΔmmHg, p &lt; 0.05) when compared to sham rats. Oral administration of CM-G in renovascular hypertensive rats reduced hypertension (126 ± 4 vs. 171 ± 11 mmHg, p &lt; 0.05) and improved the BRS (-2.03 ± 0.16 vs. -1.30 ± 0.10 bpm.mmHg-1, p &lt; 0.05) in 2K1C rats when compared to placebo. Those effects seem to be caused by a reduction in sympathetic activity. The present study revealed for the first time that CM-G treatment reduces arterial hypertension and restores arterial baroreflex sensitivity via a reduction in the sympathetic tone in conscious renovascular hypertensive rats