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(Hypertension. 2002;39:673.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Function and Regulation of Endothelin-1 and Its Receptors in Salt Sensitive Hypertension Induced by Sensory Nerve Degeneration

Diana Z. Ye; Donna H. Wang

From the Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Mich.

Correspondence to Donna H. Wang, MD, Department of Medicine, College of Human Medicine, Michigan State University, B338 Clinical Center, East Lansing, MI 48824. E-mail donna.wang{at}ht.msu.edu

To determine the role of endothelin-1 (ET-1) and its receptors in salt-sensitive hypertension induced by sensory nerve degeneration, selective ET_A antagonist (ABT-627) and ET_B antagonist (A-192621) were used. Newborn Wistar rats were given vehicle or 50 mg/kg capsaicin subcutaneously on the first and second days of life. After the weaning period, male rats were divided into eight groups, and subjected to the following treatments for 2 weeks: control + normal salt diet (Con+NS, 0.5%), control + high salt diet (Con+HS, 4%), control + high salt diet + ABT-627 (Con+HS+ABT-627), control + high salt diet + A-192621 (Con+HS+A-192621), capsaicin + normal salt diet (Cap+NS), capsaicin + high salt diet (Cap+HS), capsaicin + high salt diet + ABT-627 (Cap+HS+ABT-627), capsaicin + high salt diet + A-192621 (Cap+HS+A-192621). Both ABT-627 (5 mg/kg/d) and A-192621 (30 mg/kg/d) were given by oral gavage twice a day. Mean arterial pressure (MAP, mm Hg) was higher in Con+HS+A-192621 (141±11) than in Con+NS (94±10), Con+HS (95±5), and Con+HS+ABT-627 (97±6) (P<0.05). MAP was also higher in Cap+HS (152±6) and Cap+HS+A-192621 (180±7) than in Cap+NS (99±3) and Cap+HS+ABT-627 (104±5) (P<0.05), and it was higher in Cap+HS+A-192621 than in Cap+HS (P<0.05). Enzyme immunometric assay showed that ET-1 plasma concentration (pg/mL) was higher in Con+HS+A-192621 (7.59±0.78) than in Con+NS (2.68±0.56), Con+HS (2.50±0.92), and Con+HS+ABT-627 (3.54±0.79) (P<0.05). ET-1 plasma concentration was also higher in Cap+HS (8.95±2.16), Cap+HS+ABT-627 (9.82±1.22) and Cap+HS+A-192621 (10.97±0.57) than in Cap+NS (3.06±0.73) (P<0.05). We conclude that blockade of the ET_A receptor prevents the development of salt sensitive hypertension induced by sensory nerve degeneration, indicating that activation of the ET_A receptor by increased plasma ET-1 level contributes to elevation of blood pressure in this model. In contrast, blockade of the ET_B receptor leads to an increase in blood pressure in both normal and sensory nerve degenerated rats fed a high salt diet. These results suggest that ET_B plays an antihypertensive role in response to high salt intake under both normal and sensory nerve degenerated conditions.

Key Words: endothelin • receptors, endothelin • hypertension, sodium-dependent

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