Caveolae Dysfunction Contributes to Impaired Relaxation Induced by Nitric Oxide Donor in Aorta from Renal Hypertensive Rats

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 323; no. 3; pp. 831 - 837
• Main Authors: Rodrigues, G J, Restini, C B, Lunardi, C N, Moreira, J E, Lima, R G, da Silva, R S, Bendhack, L M
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.12.2007
• Subjects: Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Aorta, Thoracic - physiopathology; Blood Pressure - drug effects; Blood Pressure - physiology; Calcium - metabolism; Caveolae - drug effects; Caveolae - metabolism; Cells, Cultured; Disease Models, Animal; Hypertension, Renal - etiology; Hypertension, Renal - metabolism; Male; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiopathology; Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Rats; Rats, Wistar
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.107.127241

Relaxation induced by nitric oxide (NO) donors is impaired in renal hypertensive two kidney-one clip (2K-1C) rat aortas. It has been proposed that caveolae are important in signal transduction and Ca 2+ homeostasis. Therefore, in the present study we investigate the integrity of caveolae in vascular smooth muscle cells (VSMCs), as well as their influence on the effects produced by NO released from both the new NO donor [Ru(NH.NHq) (terpy)NO + ] 3+ (TERPY) and sodium nitroprusside (SNP) on 2K-1C rat aorta. The potency of both TERPY and SNP was lower in the 2K-1C aorta that in the normotensive aorta [two kidney (2K)], whereas the maximal relaxant effect (ME) was similar in both 2K-1C and 2K aortas. In the 2K aorta, methyl-β-cyclodextrin (CD) reduced both the potency of TERPY and SNP, and their ME compared with the control, but it had no effect on the potency and ME of these NO donors in 2K-1C aortas. The decrease in cytosolic Ca 2+ concentration ([Ca 2+ ] c ) induced by TERPY was larger in 2K than in 2K-1C cells, and this effect was inhibited by CD in 2K cells only. Aortic VSMCs from 2K rats presented a larger number of caveolae than those from 2K-1C rats. Treatment with CD reduced the number of caveolae in both 2K and 2K-1C aortic VSMCs. Our results support the idea that caveolae play a critical role in the relaxant effect and in the decrease in [Ca 2+ ] c induced by NO, and they could be responsible for impaired aorta relaxation by NO in renal hypertensive rats.