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, 750 ng/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 +/- 6 mmHg in anti-endothelin antibodies-treated group, n = 7 compared to 164 +/- 5 mmHg 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.
Yasujima
M
M
Institute of Rehabilitation Medicine, Tohoku University School of Medicine, Narugo, Japan.
Kanazawa
M
M
Yoshida
K
K
Kohzuki
M
M
Watanabe
H
H
Hiwatari
M
M
Sato
T
T
Abe
K
K
Hirata
Y
Y
Yoshinaga
K
K
D000375:Aging / Q000502:physiology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight; D002561:Cerebrovascular Disorders / Q000235:genetics* / Q000503:physiopathology; D003900:Desoxycorticosterone; D016232:Endothelins / Q000276:immunology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D014563:Urodynamics / Q000502:physiology
D000906:Antibodies; D016232:Endothelins; D003900:Desoxycorticosterone