DECREASED NUMBER OF CAVEOLAE IN ENDOTHELIAL CELLS IMPAIRS THE RELAXATION INDUCED BY ACETYLCHOLINE IN HYPERTENSIVE RAT AORTAS

FF04

Rodrigues, GJ (gjrodrig@fcfrp.usp.br)(1); Restini, CB (1); Lunardi, CN (1, 3);  Neto, MA (2); Moreira, JE (2); Bendhack, LM (1).

(1) Faculdade de Ciências Farmacêuticas de Ribeirão Preto, (2) Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP- Brazil, and  (3) Faculdade de Ceilândia, Universidade de Brasília, DF-Brazil.

Endothelium-dependent relaxation induced by acetylcholine is impaired in renal hypertensive two kidney-one clip (2K-1C) rat aortas. It has been proposed that endothelial caveolae are important to the synthesis of nitric oxide (NO). The present study aimed to investigate the contribution of the endothelial cells caveolae to the endothelium dependent relaxation and their integrity in endothelial cells from 2K-1C rat aortas. The potency and the maximal relaxant effect (ME) of acetylcholine were greater in 2K than in 2K-1C aortas. The caveolae disassembler methyl-b-cyclodextrin (CD) reduced the potency and ME to acetylcholine in 2K. However, CD did not modify the potency but it reduced ME of acetylcholine in aortas from 2K-1C. NO production stimulated with acetylcholine was greater in 2K than in 2K-1C endothelial cells. CD impaired the NO production in endothelial cells from 2K-1C and 2K. We verified that the increase of cytosolic Ca²⁺ concentration ([Ca²⁺]c) induced by acetylcholine in endothelial cells was  higher in 2K than in 2K-1C, which was impaired by CD only in 2K. Acetylcholine decreased [Ca²⁺]c in the vascular smooth muscle cells, which response was higher in 2K than in 2K-1C. CD impaired this response only in 2K. We have quantified a larger number of caveolae in the endothelial cells from 2K than in 2K-1C rats. Moreover, CD reduced the number of caveolae in both 2K and 2K-1C endothelial cells. Our results support the hypothesis that the integrity of endothelial cells caveolae plays an important role in the NO production induced by acetylcholine in 2K-1C endothelial cells.