Abstract
The vasodilatory effect of VEGF has not been characterized in the setting of hypertension. This study investigated the in vitro vasorelaxant effects of VEGF in organ chambers in the aorta of the adult (12-week-old) spontaneously hypertensive rats (SHR), young (4-week-old) SHR without hypertension, and age-matched Wistar-Kyoto (WKY) rats compared with acetylcholine (ACh). Cumulative concentration-relaxation curves were established for VEGF (∼10−12–10−8.5 M) and ACh (∼10−10–10−5 M) in U46619(10−8 M)-induced contraction. VEGF induced endothelium-dependent relaxation that was significantly reduced in the adult SHR compared with the age-matched WKY control (87.8 ± 2.8 versus 61.4 ± 8.6%, P = 0.01). These responses were significantly attenuated by pretreatment withN ω-nitro-l-arginine (l-NNA, 300 μM) alone (SHR: 25.1 ± 1.9%; WKY: 21.0 ± 2.6%; P = 0.01) or indomethacin (7 μM) + l-NNA (SHR: 30.2 ± 2.1%; WKY: 35.0 ± 2.9%; P = 0.01). Further addition of oxyhemoglobin (20 μM) abolished the residual relaxation and reduced the relaxation induced by nitroglycerin. ACh induced similar responses to VEGF. In contrast, pretreatment with indomethacin alone enhanced VEGF- or ACh-induced relaxations and the effect was greater in the adult SHR than in WKY rats. In contrast to the adult SHR versus WKY rats, there were no significant differences of VEGF- or ACh-induced relaxations between young SHR and WKY rats. The results demonstrate that VEGF induces endothelium- or nitric oxide-dependent relaxation, which is blunted in the adult SHR. The mechanism of this impairment may be related to decreased release of NO although increased release of contracting factors from the dysfunctional endothelium may also be involved.
Footnotes
- Received June 6, 2000.
- Accepted October 5, 2000.
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Send reprint requests to: Professor Guo-Wei He, Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Block B, 5A, Prince of Wales Hospital, Shatin, N. T., Hong Kong SAR, China. E-mail: gwhe{at}cuhk.edu.hk
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This study was supported by Providence St. Vincent Medical Foundation, Portland, OR, and Hong Kong Research Grants Council grants (CUHK7280/97 M and CUHK7246/99 M). Dr. Liu is a Starr-He International Postdoctoral Fellow.
- The American Society for Pharmacology and Experimental Therapeutics
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