ET(A) receptor antagonist prevents blood pressure elevation and vascular remodeling in aldosterone-infused rats.

Abstract

Increased endothelin-1 may be associated with elevation of blood pressure (BP) and promotion of vascular hypertrophy, especially in salt-sensitive hypertension. Mineralocorticoid hypertension has been associated with activation of the endothelin system. We evaluated whether in aldosterone-infused rats the selective endothelin type A receptor-antagonist BMS 182874 prevents BP elevation and vascular hypertrophy. Rats were infused with aldosterone (0.75 microg/h) subcutaneously via a mini-osmotic pump and were offered 1% NaCl in the drinking water+/-BMS 182874 (40 mg/kg in food) for 6 weeks. Systolic BP was monitored by the tail-cuff method, and vascular changes of mesenteric arteries were evaluated using a pressurized myograph. Aldosterone-infusion significantly increased BP to 151+/-7 mm Hg compared with controls (108+/-4 mm Hg, P<0.01). BMS 182874 normalized BP (117+/-4 mm Hg). Media cross-sectional area of aorta was significantly increased by aldosterone infusion (P<0.05), and BMS treatment normalized it (P<0.001). Aldosterone infusion increased media width and media-to-lumen ratio of mesenteric resistance arteries (17.6+/-0.4 microm and 7.5+/-0.4%) compared with controls (14.2+/-0.5 microm, P<0.01, and 5.9+/-0.1%, P<0.05). BMS 182874 normalized media and media-to-lumen ratio (15.1+/-0.6 microm and 5.7+/-0.1%, both P<0.01). In conclusion, the endothelin type A receptor antagonist attenuated BP elevation and prevented vascular remodeling or hypertrophy of aorta and mesenteric resistance arteries in aldosterone-infused rats. These results suggest a role for endothelin-1 in BP elevation and structural alterations of large and small vessels in aldosterone and salt-induced hypertension.

• Authors: J B Park, E L Schiffrin
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 37 Issue 6 Pg. 1444-9 (Jun 2001) ISSN: 1524-4563 [Electronic] United States
• PMID: 11408393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Dansyl Compounds
• Endothelin Receptor Antagonists
• Endothelin-1
• Endothelins
• Protein Precursors
• RNA, Messenger
• Receptor, Endothelin A
• 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide
• Aldosterone
• Potassium

Topics

• Aldosterone (administration & dosage)
• Animals
• Antihypertensive Agents (therapeutic use)
• Aorta (drug effects, metabolism, pathology)
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Dansyl Compounds (therapeutic use)
• Endothelin Receptor Antagonists
• Endothelin-1
• Endothelins (biosynthesis, blood, genetics)
• Hypertension (chemically induced, drug therapy, pathology, physiopathology)
• Hypertrophy (chemically induced, drug therapy, pathology)
• Infusions, Parenteral
• Male
• Mesenteric Arteries (drug effects, pathology, physiopathology)
• Potassium (blood)
• Protein Precursors (biosynthesis, genetics)
• RNA, Messenger (biosynthesis)
• Rats
• Rats, Sprague-Dawley
• Receptor, Endothelin A
• Vasoconstriction (drug effects)
• Vasodilation (drug effects)