Improvement of organ damage by a non-depressor dose of imidapril in diabetic spontaneously hypertensive rats

Abstract

Many clinical trials have demonstrated that angiotensin converting enzyme inhibitors have protective effects on organ damage, suggesting the importance of inhibition of the renin-angiotensin system. In this study, we investigated the effects of a non-depressor dose of imidapril on organ damage induced by diabetes and hypertension. Diabetes was induced by an intravenous injection of streptozotocin (STZ, 40 mg/kg) in 15-week-old male spontaneously hypertensive rats (SHR). Imidapril (2 mg/ kg/day) or vehicle was given orally for 28 days, and then the heart weight, left ventricle mass (LVM), urinary albumin excretion (UAE) and endothelial function were examined, as well as the urinary NOx level and local hepatocyte growth factor (HGF) expression. There were no significant differences between the treated groups in systolic blood pressure and plasma parameters. On the other hand, UAE was significantly suppressed in the imidapril-treated group (450±44 mg/day) compared to the vehicle-treated group (963±182 mg/day) (p<0.01). Moreover, endothelial function assessed by dilative reaction to acetylcholine as well as cardiac hypertrophy assessed by both heart/body weight ratio and LVM were significantly improved in the imidapriltreated group (p<0.05 and p<0.01, respectively). The urinary NOx concentration and local HGF expression in vessel walls were also significantly increased in the imidapril-treated group (p<0.01). A non-depressor dose of imidapril showed protective effects against organ damage in diabetic SHR, which may be partially due to the increase of HGF and NO.

Inhibition of experimental abdominal aortic aneurysm progression by nifedipine

“…The aortic size was measured before and after laparotomy once per week up to 4 weeks after the operation. Blood pressure was measured in pre-warmed rats by the tail-cuff method (BP-98A; Softron Co., Tokyo, Japan) as previously reported (27).…”

A heptameric peptide purified from Spirulina sp. gastrointestinal hydrolysate inhibits angiotensin I-converting enzyme- and angiotensin II-induced vascular dysfunction in human endothelial cells

“…In particular, it plays a key role in the pathology of hypertension ( 3 ). In the renin-angiotensin system, angiotensin I (Ang I)-converting enzyme (ACE) hydrolyzes the inactive decapeptide Ang I by cleaving a dipeptide from the C-terminus to produce the potent vasoconstrictor Ang II, which is responsible for increasing arterial pressure ( 4 , 5 ). Therefore, the modulation of the renin-angiotensin system has become a promising approach for controlling blood pressure in the treatmente of cardiovascular disorders, for example by using ACE inhibitors as therapeutic agents.…”

Nicorandil Ameliorated Hypertensive Renal Injury without Lowering Blood Pressure in Spontaneously Hypertensive Rats

“…First, nitric oxide production through eNOS is critical for protection, since (1) eNOS in the kidney is mainly expressed in the renal vascular endothelium, such as glomerular capillaries and renal arteries and arterioles, but not in cortical capillaries or venous endothelium [21] , although subtle tubular expression of eNOS also occurs in locations such as the inner medullary collecting duct [22] and the thick ascending limb of loop of Henle [23] and (2) nitric oxide plays an important role in the control of renal function through multiple mechanisms such as increasing renal blood flow by vasodilatation, increasing glomerular filtration rate [24] , and protecting the endothelium via its antiapoptotic effects. For instance, a nonhypotensive dose of an ACE inhibitor in diabetic SHR was shown to inhibit proteinuria through an increase in nitric oxide production via elevation of eNOS activity, and to result in an increase in urinary excretion of NOx [25] . On the other hand, genetic or pharmacologic inhibition of eNOS is reported to lead to development of renal abnormalities, including tubular cell death in eNOS knockout mice [26] and in nitro-L -arginine methyl estertreated subtotally nephrectomized rats [27] .…”