Statins boost beneficial pleiotropic cardiovascular effects of cilostazol in angiotensin-II hypertensive rats

Abstract

Background and aims: Hypertension is a major cause of cardiovascular (CVS) diseases. Statins exhibit a blood pressure-lowering effect independent of cholesterol. This study investigates whether combining statins with the phosphodiesterase-III inhibitor cilostazol enhances antihypertensive and cardioprotective effects.

Methods: Hypertension was induced in rats via implanted mini-osmotic pumps releasing angiotensin II at 120 ng.kg^-1.min^-1 for 11 days. Hypertensive rats were treated with cilostazol (50 mg.kg^-1.day^-1), rosuvastatin (20 mg.kg^-1.day^-1), atorvastatin (50 mg.kg^-1.day^-1), or their combinations for seven days. Cardiovascular parameters, baroreflex sensitivity, histopathology, myocardial injury markers (creatine kinase-MB "CK-MB" and cardiac troponin I "cTnI"), and oxidative stress (catalase and malondialdehyde "MDA") were evaluated.

Results: Cilostazol reduced systolic blood pressure, improved left ventricular (LV) function, and mitigated baroreflex dysfunction. Co-administration of atorvastatin enhanced these effects, with rosuvastatin showing greater improvements. The rosuvastatin/cilostazol combination significantly reduced myocardial injury, oxidative stress, and histopathological damage in the heart and aorta.

Conclusion: Statins, particularly rosuvastatin, enhanced cilostazol's antihypertensive and cardioprotective effects, highlighting the potential of this combination in managing hypertension and CVS diseases.

Keywords: Baroreflex; Cilostazol; Hypertension; Statins; Ventricular dysfunction.