EXPRESIÓN Y PARTICIPACIÓN FUNCIONAL DE LOS RECEPTORES DOPAMINÉRGICOS D1 Y D3, EN ANILLOS DE AORTA DE RATA CON HIPERTENSIÓN ARTERIAL SISTÉMICA ESPONTÁNEA.

Abstract

There are reports that show the presence of dopamine receptors D1 and D3 in different vascular beds, its location and function are controversial, also is not further clarified their participation in a disease such as hypertension. In this work we decided to study the effect of D1 and D3 dopamine receptor activation, in rat aortic rings with spontaneous hypertension. Aortic rings were obtained from male rats (SHR-spontaneously hypertensive, WK - Wistar Kyoto and SD-Sprague Dawley), which were placed in a perfusion chamber, basal tension was adjusted to 2 g and concentration response curves were performed in aortic rings, in presence or not of phenylephrine. Dopamine agonists (SKF-38 393 D1-, D3-7 -OH-DPAT, 10-9 to 10-4 M) were tested in aortic rings with endothelium (EC) and without endothelium (SE). Same protocols were performed in the presence of dopamine antagonists (D1-SCH-23 390, D3-U-99194A, 10-5 M), respectively. Another group of rats underwent removal of the thoracic aorta and Western blot assay was made to verify the presence of D1 and D3 dopamine receptors. The results show that 7-OH-DPAT produced vasoconstriction in aortic rings CE and SE, dose-dependent effect in the 3 strains rats used, which was significantly lower in SH rats with the highest concentration used compared with WK and SD rats, where the effect was similar. This vasoconstriction effect was significantly less in the presence of the specific antagonist of the D3 dopamine receptor (U-99194A). The SKF-38393 in rings precontracted with phenylephrine, showed a vasodilator effect in aortic rings CE and SE 71% and 56%, respectively, being the greater effect in SH rats at the highest dose used, when compared with SD and WK rats. The relaxation effect was decreased in the presence of the specific antagonist of the D1 dopamine receptor (SCH-23390) in SH rats, close to 15% at maximum effect observed. It was confirmed the expression of dopamine receptors D1 and D3 with the Western blot assays in the aorta tissues studied. These results suggest that D1 and D3 dopamine receptors are present in the aorta tissues from SD, WK and SHR rats. D1 receptor activation induces a relaxation effect and was increased in hypertensive rats. D3 receptor activation causes vasoconstriction and this effect was less in hypertensive rats. This suggests an up-regulation for D1 and down-regulation for D3 dopamine receptors in order to maintain a balance of blood pressure in hypertensive rats.