Effects of pergolide on blood pressure and tissue injury in DOCA-salt hypertension.
The present study was designed to evaluate the possible antioxidant effect of pergolide, a DA-2 receptor agonist, in deoxycorticosterone acetate (DOCA)-salt hypertension and its role in endogenous endothelin-1 (ET- 1) production and organ hypertrophy. Male Sprague-Dawley rats were uninephrectomized (UNx) or uninephrectomized, and received subcutaneous implants of DOCA and drank 1% sodium chloride (DOCA). DOCA rats were treated daily for 3 weeks with pergolide (1 mg/kg, i.p.) or vitamin C (1 mg/rat, orally). DOCA-salt treatment increased systolic blood pressure (SBP) in UNx rats by 45 +/- 2 mmHg from 117 +/- 5 to 162 +/- 10 mmHg (p < 0.05), an effect blunted by pergolide and vitamin C. Superoxide generation was not increased in DOCA rats; however, both pergolide and vitamin C significantly reduced superoxide generation by 49 +/- 7% and 52 +/- 13%, respectively (p < 0.05). Plasma ET-1 levels increased twofold in UNx rats but was reduced to 42 +/- 7% (p < 0.05) in DOCA compared to UNx rats. Pergolide and vitamin C reduced plasma ET-1 levels further by 43 +/-10% (p < 0.05) and 46 +/- 8% (p < 0.05), respectively. Pergolide increased urinary Na+ excretion but did not alter urinary protein excretion or the left ventricular and aortic hypertrophy in DOCA rats. These data suggest that the reduction of SBP by pergolide in DOCA-salt hypertension may be attributed to its natriuretic ability, not its ability to reduce superoxide generation or ET- 1 production.
Newaz
Mohammad A
MA
Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston 77004, USA.
Yousefipour
Zivar
Z
Oyekan
Adebayo
A
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000633:toxicity; D018491:Dopamine Agonists / Q000627:therapeutic use; D019332:Endothelin-1 / Q000096:biosynthesis; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010479:Pergolide / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D018491:Dopamine Agonists; D019332:Endothelin-1; D013481:Superoxides; D010479:Pergolide; D003900:Desoxycorticosterone; D001205:Ascorbic Acid