Year-Long Antihypertensive Therapy With Candesartan Completely Prevents Development of Cardiovascular Organ Injuries in Spontaneously Hypertensive Rats

Abstract

SummaryMost previous studies have examined the effects of antihypertensive drugs in hypertensive animals for only a few months, and little information has been provided as to the protective effects of lifetime antihypertensive medication against cardiovascular organ injury. In this study, spontaneously hypertensive rats (SHR) were treated for 1 year with an angiotensin-II receptor antagonist (ARB) and the development of hypertensive organ injury was evaluated. Male 15-week-old SHR (n = 9) were given 25 mg/L candesartan (CS) in their drinking water for 1 year. Twelve SHR and 9 normotensive Wistar-Kyoto rats (WKY) were given normal tap water. Tail-cuff blood pressure was almost normalized by CS throughout 1 year (at 12-months: WKY 132 ± 3, SHR 229 ± 3, CS 137 ± 4 mmHg). After 1 year, cardiac ventricular weight (SHR +33%, CS -2% versus WKY) and aortic thickness (SHR +34%, CS +4% versus WKY) in the CStreated SHR rats were not different than those of WKY. Echocardiographic midwall fractional shortening (SHR -18%, CS -1% versus WKY) and left ventricular hydroxyproline content (SHR +47%, CS +11% versus WKY) were also improved by CS to the WKY level. With respect to kidney function, GFR (SHR -24%, CS +9% versus WKY) was preserved, proteinuria (SHR +312%, CS +12% versus WKY) was reduced, and the histological glomerular injury rate (SHR +186%, CS +6% versus WKY) was reduced by CS. These results suggest that long-term antihypertensive therapy with CS can completely prevent hypertensive cardiovascular and renal injuries in SHR. (Int Heart J 2010; 51: 359-364)

The protective effects of ginsenoside Rg1 against hypertension target-organ damage in spontaneously hypertensive rats

“…To delay or prevent hypertension target-organ, containing heart failure and renal failure, is essential to improve patient’s quality of life [26]. In agreement with previous reports that the most common change found in large arteries in hypertension is an “outward hypertrophic remodeling”, we detected the increased lumen diameter and wall thickness in SHR compared with WKY.…”

“…The final goal of novel therapy of hypertension is not only to normalize the blood pressure level but also to prevent end-organ damage, such as cardiac hypertrophy and renal dysfunction [26,34]. Altered retinal arteries diameter has also been demonstrated to be associated with heart failure, suggesting that evaluation of the retinal microvasculature may be a useful predictor of target organ damage [35,36].…”

AMP-activated protein kinase activator AICAR acutely lowers blood pressure and relaxes isolated resistance arteries of hypertensive rats

“…4-20 mmHg) [2,3], and the ability of these studies to delineate significant BP reductions in normotension may be due to use of higher doses of AICAR [2], different experimental protocols [2,3], or human vs. animal models [3]. Although in-vivo hemodynamic responses can be affected by the anesthetic regime utilized during experimental protocols and should be interpreted in this context, HRs and baseline BPs of the anesthetized animals in our study are comparable to those of conscious animals [24,25] instilling confidence in the integrity and validity of the hemodynamic measurements and treatment responses represented.…”

Renoprotective effects of stevia (Stevia rebaudiana Bertoni), amlodipine, valsartan, and losartan in gentamycin-induced nephrotoxicity in the rat model: Biochemical, hematological and histological approaches

“…Amlodipine, a calcium (Ca 2+ ) channel blocker, showed antithrombotic, and antiatherosclerotic effects, were not dependent on modulation of L-Type calcium channels [13]. Relaxation of arteriolar smooth muscle and decreasing the peripheral vascular resistance can reduce the blood pressure due to the action of CCB [14]. The protective effects of CCBs against gentamycin-induced nephrotoxicity is assumed to be mediated through the inhibition of intracellular calcium release [10,[15], [16], [17]].…”