Gender dichotomy in reactivity to the vasoactive oxidant hydrogen peroxide in spontaneously hypertensive rats

To determine: 1) whether ovariectomy increases low-density lipoprotein (LDL) cholesterol; 2) if increased LDL cholesterol correlates with increased blood pressure; and 3) whether arterial muscle reactivity to the vasoactive oxidant hydrogen peroxide (H2O2) is gender-dependent in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY).

SHR and WKY females were ovariectomized at four weeks of age. Blood pressures were monitored weekly. Blood was collected at the time of sacrifice at 16-18 weeks, and caudal arteries were excised. LDL cholesterol was measured. Caudal arterial muscle was contracted with high-calcium egtazic acid (EGTA)/ionomycin (calcium ionophore) and relaxed with zero-calcium EGTA/ionomycin. H2O2-induced contractions were elicited in zero calcium. H2O2 reactivity was compared for SHR and WKY, male and female arterial muscle.

Ovariectomy increased LDL cholesterol in both SHR and WKY but blood pressure increased only in SHR. Male SHR and WKY arterial muscle was more reactive to H2O2 compared with female preparations.

Gender dichotomy in the development of hypertension does not appear to be due directly to the LDL-lowering effects of estrogen but is likely due, at least in part, to lower arterial reactivity to vasoactive oxidants, such as H2O2, with a consequent reduction of oxidant-induced vasoconstriction in female SHR.