Chronic Treatment with Anti-Endothelin Antibodies Fails to Modify the Development of Hypertension in Stroke-Prone Spontaneously Hypertensive Rats and DOCA-Salt Hypertensive Rats

This study was designed to assess whether blocking endogenous endothelin with anti-endothelin antibodies could alter the development of hypertension in stroke-prone spontaneously hypertensive rats (SHR) and DOCA-salt treated rats. Specific anti-endothelin antibodies were produced in rabbits by standard methods. The amount of anti-endothelin antibodies employed in this study blocked the hypertensive effect of endothelin-1, 750ng/kg, by 55% in conscious rats. Intravenous injection of anti-endothelin antibodies as a bolus twice a week for 3 weeks did not affect the rise in blood pressure of stroke-prone SHR (268±8 mmHg, n=8) compared to control stroke-prone SHR (256±7 mmHg, n=8) treated with normal rabbit serum. Intravenous administration of anti-endothelin antibodies in a same manner also failed to alter the development of hypertension in DOCA-salt treated rats (160±6mmHg in anti-endothelin antibodies-treated group, n=7 compared to 164±5mmHg in normal rabbit serum-treated group, n=7). The administration of anti-endothelin antibodies did not induce any significant changes in body weight, urine volume and urinary sodium excretion in stroke-prone SHR and DOCA-salt treated rats compared to those treated with normal rabbit serum. These findings suggest that circulating endothelin might not play a major role in the regulation of blood pressure in stroke-prone SHR and DOCA-salt treated rats.