Effect of 17beta-oestradiol replacement on vascular responsiveness in ovariectomized diabetic rats.Clin Exp Pharmacol Physiol. 2009 Nov; 36(11):e65-71.CE
1. Women with functional ovaries exhibit a gender advantage in terms of the prevalence of cardiovascular diseases. However, whether this gender bias pertains in diabetes is unknown. 2. The aim of the present study was to examine the effects of 17beta-oestradiol (E2) on vascular responsiveness in normal and diabetic ovariectomized (OVX) rats. Aged-matched female rats were divided into four groups as follows: (i) OVX; (ii) OVX + E2 treated; (iii) diabetic OVX; and (iv) diabetic OVX + E2 treated. Bilateral ovariectomy was performed and streptozotocin was used to induce experimental diabetes. Rats were treated with 1 mg/kg per day, p.o., E2 for 8 weeks. 3. Although E2 treatment had no effect on blood glucose levels in normal and diabetic OVX rats, it significantly reduced systolic blood pressure and prevented diabetes-induced loss of bodyweight gain. 4. In segments of the thoracic aorta, concentration-dependent vasoconstrictor responses to KCl and phenylephrine were significantly attenuated following E2 treatment in both the normal and diabetic groups. The sarcoplasmic/endoplasmic reticulum calcium ATPase inhibitor thapsigargin (10(-6) mol/L) and the Ca(2+) channel blocker nifedipine (10(-6) mol/L) inhibited the transient vasoconstriction to PE in all groups. The constrictor effect of PE was increased by the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME; 10(-6) mol/L), but was reduced by superoxide dismutase (SOD; 100 U/mL) and the cyclo-oxygenase inhibitor indomethacin (10(-6) mol/L) in all groups. Responses to acetylcholine (ACh; 10(-6) mol/L) demonstrated reduced endothelium-dependent relaxation in non-E2-treated groups. Relaxation responses to ACh were increased by 100 U/mL SOD and 10(-6) mol/L indomethacin, but were reduced by 10(-6) mol/L l-NAME in all groups. There were no differences among the four groups in terms of relaxation responses to sodium nitroprusside (10(-11) to 10(-6) mol/L). 5. In conclusion, the results of the present study suggest that oestrogen treatment has beneficial effects on vascular function in both diabetic and non-diabetic OVX rats due to Ca(2+) regulation and anti-oxidation.