Protective Effects of Olmesartan and Azelnidipine against Cardiovascular Organ Injuries in Spontaneously Hypertensive Rats

In the treatment of hypertension, care should be taken for preventing of hypertensive organ injuries as well as lowering blood pressure to the adequate level in order to reduce the risk of cardiovascular diseases. The purpose of this study is to examine the effects of angiotensin II receptor blockers (ARB), calcium channel blockers (CCB) and their combination on the development of cardiovascular organ injuries in spontaneously hypertensive rats (SHR). Four groups of male 8-week-old SHR (n=9 each) were given vehicle(control), 10 mg/kg azelnidipine (AZL), 10 mg/kg olmesartan (OLM, n=9), or the combination of AZL and OLM(5 mg/kg each)for 12 weeks, and their effects on cardiovascular organ injuries were evaluated. Tail-cuff blood at 12 weeks was similarly lowered by AML, OLM and the combination therapy(148, 143 and 143 mmHg, respectively)as compared with the control SHR (198 mmHg). Pulse rate was significantly less in the AZL group but not in the OLM group or the combination therapy group than in the untreated control group (-27, -12, +6 bpm, respectively). The cardiac ventricular weight (AZL -12%, OLM -15%, combination -18% vs. control) and aortic thickness (AZL -17%, OLM -16%, combination -19% vs. control) were reduced by similar extents in the three groups given antihypertensive treatments. Regarding the myocardial fibrosis, left ventricular hydroxyproline content was reduced in the OLM and the combination groups but the change was not significant in the AZL group (AZL -14%,OLM -30%, combination -27% vs. control). In the echocardiographic evaluation of cardiac function, the index of left ventricular diastolic function is significantly improved in the OLM and the combination groups but not in the AZL group, while the index of systolic function was not different between the four groups. It is suggested that the antihypertensive therapy including ARB is superior to the monotherapy by CCB in preventing the myocardial fibrosis and preserving the left ventricular diastolic function