Angiotensin 1-7: A Second Window of Protection in Hypertensive Patients

The effects of the renin-angiotensin-aldosterone system on the human body are so diverse and our knowledge about them is ever growing. Angiotensin 1-7 has been proven to play protective roles in patients with cardiovascular disorders including but not limited to hypertension. As is the case with Africa, the prevalence of hypertension in Sudan is rising, and its complications could be delayed by pharmacologically manipulating the levels of renin-angiotensin system metabolites. The aim of this review is to compare the advantageous and deleterious effects of Angiotensin 2 in contrast to those of Angiotensin 1-7 and to assert the well-established protective effects of Angiotensin 1-7 (systemically and locally) in hypertensive patients

Evidence for enhanced eNOS function in coronary microvessels during the second window of protection

Nitric oxide (NO) derived from endothelial NO synthase (NOS) (eNOS) has been identified as a trigger for the second window of protection (SWOP), but its role as a mediator during the SWOP is a matter of debate. Eighteen mongrel dogs were chronically instrumented to measure left ventricular function, coronary blood flow, and wall thickening. Myocardial preconditioning was induced by 10 min coronary artery occlusion. After 24 h of reperfusion (during the SWOP), the hearts were excised. Coronary microvessels were isolated and incubated in presence of 1) the endothelium-dependent agonists carbachol and bradykinin, 2) the calcium ionophore A23187, and 3) the angiotensin-converting enzyme (ACE) inhibitors enalaprilat and ramiprilat. Nitrite, a metabolite of NO, was measured. Under baseline conditions, nitrite production in microvessels from SWOP was 30% higher than that from normal (96 ± 4 vs. 74 ± 3 pmol/mg, P < 0.01, respectively). Nitrite production in response to carbachol, bradykinin, and A23187 was also enhanced in microvessels from SWOP ( P < 0.05). These enhanced responses were abolished by NG-nitro-l-arginine methyl ester (l-NAME) or the endothelial receptor-specific antagonists atropine and HOE-140. The level of eNOS protein in the SWOP myocardium was twofold higher than that in the non-SWOP myocardium. Nitrite production in response to the ACE inhibitors was greater in microvessels from SWOP. These effects were blocked by l-NAME, HOE-140, or dichloroisocoumarin (which inhibits kinin formation). We found that a brief ischemic episode induced delayed, enhanced NO production in coronary microvessels and an upregulation of eNOS protein. These findings suggest that eNOS is a mediator during the SWOP. The ability of ACE inhibitors to enhance NO release during the SWOP points to an additional clinical application for these drugs.

Kinetics Study of Endogenous Heat Shock Protein 70 Expression

The purpose of this study was to determine the kinetics of HSP70 expression in response to mild thermal stress. The rationale is to produce a basis for design of optimal heating methods to induce HSP70 expression for preconditioning in cardiac surgery. Bovine aortic endothelial cells were heated at 42°C for 0.5 to 5 hours followed by 37°C recovery for 1 to 48 hours. Quantitative analysis of western blot results showed HSP70 expression kinetics is a coupled function of heating temperature and time and of post-heating duration. Bimodal HSP70 expression kinetics were identified which may be an important cause of the “second window of protection” observed by other researchers.