Chronological Changes of .ALPHA.-Adrenoceptor-Mediated Vascular Constriction in Otsuka-Long-Evans-Tokushima Fatty Rats

Abstract

In recent years, it has been suggested that many factors are involved in the development of hypertension accompanying insulin resistance. Because changes in vascular reactivity could be one of these factors, we here investigated chronological changes of alpha-adrenoceptor (AR)-mediated peripheral arteriolar vasoconstriction in a rat model of type II diabetes. Otsuka-Long-Evans-Tokushima fatty (OLETF) rats that naturally develop insulin resistance at the age of 16 weeks and type II diabetes at the age of 30 weeks (DM group) and control rats (N group) were used. Arterioles with a diameter of approximately 100 microm were removed from the cremaster muscle of 8-, 16- and 40-week-old rats and their diameters were measured in a tissue bath. The concentration-response curve (CRC) was determined for phenylephrine and UK14,304 both with and without N(G)-monomethyl-L-arginine (LNMMA). Although there were no significant differences in the CRC for phenylephrine between the 8-week-old DM group and N group, a leftward shift was seen for the 16- and 40-week-old DM groups. There were no significant differences in the CRC for UK14,304 between the two groups at any age, but in the presence of LNMMA, a leftward shift was seen in the 8- and 16-week-old but not in the 40-week-old DM groups. One possible explanation for these results is that impaired endothelium-dependent dilatation may have offset the reduction in arteriolar smooth muscle contraction. In conclusion, in the OLETF rats, the sensitivity of alpha-AR-mediated arteriolar vasoconstriction increased after the onset of insulin resistance. The sensitivity of alpha2-AR-mediated arteriolar smooth muscle contraction and endothelium-dependent vascular relaxation were both presumed to be impaired after the onset of type II diabetes.