Renin-Angiotensin System Blockade Improves Endothelial Dysfunction in Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 36; no. 4; pp. 575 - 580
• Main Authors: Goto, Kenichi, Fujii, Koji, Onaka, Uran, Abe, Isao, Fujishima, Masatoshi
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.10.2000; Hagerstown, MD Lippincott
• Subjects: Acetylcholine - metabolism; Acetylcholine - pharmacology; Administration, Oral; Angiotensin Receptor Antagonists; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antihypertensive agents; Antihypertensive Agents - administration & dosage; Benzimidazoles - administration & dosage; Biological and medical sciences; Biological Factors - metabolism; Biphenyl Compounds - administration & dosage; Cardiovascular system; Cromakalim - administration & dosage; Disease Models, Animal; Drug Therapy, Combination; Enalapril - administration & dosage; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Enzyme Inhibitors - administration & dosage; Hypertension - drug therapy; In Vitro Techniques; Indomethacin - pharmacology; Male; Medical sciences; Nitroarginine - pharmacology; Norepinephrine - metabolism; Norepinephrine - pharmacology; Pharmacology. Drug treatments; Potassium Channels - drug effects; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System - drug effects; Tetrazoles; Peptides; Rat; Cardiovascular disease; Enalapril; Endothelium derived relaxing factor; Angiotensin II; Vascular wall; Biological receptor; Hypertension; Treatment efficiency; Rodentia; Exploration; Endothelium; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Antihypertensive agent; Combined treatment; Angiotensin antagonist; Hemodynamics; ACE inhibitor; Comparative study; Hyperpolarization
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.36.4.575

Angiotensin-converting enzyme (ACE) inhibitor improves the impaired hyperpolarization and relaxation to acetylcholine (ACh) via endothelium-derived hyperpolarizing factor (EDHF) in arteries of spontaneously hypertensive rats (SHR). We tested whether the angiotensin type 1 (AT1) receptor antagonist also improves EDHF-mediated responses and whether the combined AT1 receptor blockade and ACE inhibition exert any additional effects. SHR were treated with either AT1 receptor antagonist TCV-116 (5 mg · kg · d) (SHR-T), enalapril (40 mg · kg · d) (SHR-E), or their combination (SHR-T&E) from 8 to 11 months of age. Age-matched, untreated SHR (SHR-C) and Wistar Kyoto (WKY) rats served as controls (n=8 to 12 in each group). Three treatments lowered blood pressure comparably. EDHF-mediated hyperpolarization to ACh in mesenteric arteries in the absence or presence of norepinephrine was significantly improved in all treated SHR. In addition, the hyperpolarization in the presence of norepinephrine was significantly greater in SHR-T&E than in SHR-E (ACh 10 mol/L with norepinephrineSHR-C −7; SHR-T −19; SHR-E −15; SHR-T&E −22; WKY −14 mV). EDHF-mediated relaxation, assessed in the presence of indomethacin and N-nitro-l-arginine, was markedly improved in all treated SHR. Hyperpolarization and relaxation to levcromakalim, a direct opener of ATP-sensitive K-channel, were similar in all groups. These findings suggest that AT1 receptor antagonists are as effective as ACE inhibitors in improving EDHF-mediated responses in SHR. The beneficial effects of the combined AT1 receptor blockade and ACE inhibition appears to be for the most part similar to those of each intervention.