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

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.