Atherosclerosis is the leading cause of vascular disease worldwide and contributes significantly to deaths from cardiovascular complications. There is a remarkably close relationship between atherosclerotic plaque formation and the activation of renin-angiotensin system (RAS). However, depending on which RAS pathway is activated, pro-or anti-atherogenic outcomes may be observed. This brief review focuses on the role of three of the most important pieces of RAS axis, angiotensin II (Ang-II), angiotensin converting enzyme type 2 (ACE2), and angiotensin 1-7 (Ang-1-7) and their involvement in atherosclerosis. We focused on the effects of these molecules on vascular function and inflammation, which are important determinants of atherogenesis. Furthermore, we highlighted potential pharmacological approaches to treat this disorder.

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 < 0.05), impaired BRS (-1.30 ± 0.10 vs. -2.59 ± 0.17 bpm.mmHg-1, p < 0.05) and enhanced sympathetic activity as shown by the hexamethonium test (-60 ± 5 vs. -33 ± 2 ΔmmHg, p < 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 < 0.05) and improved the BRS (-2.03 ± 0.16 vs. -1.30 ± 0.10 bpm.mmHg-1, p < 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.

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 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 6 weeks after the induction of 2K1C hypertension, oral treatment with the HEX (10 mg/Kg/day) for 7 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.

No abstract

No abstract