Effect of tempol on myocardial vascular remodeling in female spontaneously hypertensive rats

Abstract

Objective: The present study evaluated whether the treatment with the superoxide anion dismutase mimetic tempol prevents the worsening in hypertension and in myocardial vascular remodeling induced by ovariectomy in female spontaneously hypertensive rats (SHR). Methods: Experiments were performed in ten week old female SHRs randomly assigned to the groups: intact (INT: given vehicle; INT+T: treated with tempol, 90 mg/kg/day), ovariectomized (OVX: vehicle and OVX+T: tempol, respectively) and ovariectomized treated with 17ß-estradiol (OVX+E2 and OVX+E2+T). Evolution of systolic blood pressure (SBP) was determined every other week in lightly restrained awake rats using a noninvasive computerized tail-cuff plethysmography system. At 18 weeks of age the heart was excised and structural changes in histopathological sections of coronary vessels were quantified on a computerized imaging system analyzer. Results: SBP was significantly lower in female SHRs treated with tempol compared to the values measured in untreated animals. In the vascular remodeling of myocardial arterioles, OVX+T rats had a lower media cross sectional area and media-to-lumen ratio than those observed in the OVX SHR. Interestingly, treatment with tempol in the presence of estradiol (in female INT and OVX+E2 SHR ) increased media cross sectional area and wall-to-lumen ratio of myocardial arterioles, despite the fact that it lowered arterial pressure in those groups. Conclusions: These results indicate that tempol prevents arterial hypertension and blunts myocardial vascular remodeling in ovariectomized SHR. Paradoxically, when tempol is given in presence of estradiol it has a detrimental effect on myocardial arteriolar remodeling