Time-dependent changes in the vasoconstrictor responses in diabetic rats

ABSTRACT

Disturbed vascular reactivity is one of the cardinal complications of diabetes mellitus [DM]. Several mechanisms have been postulated to explain changes in vascular responses associated with DM such as altered intracellular calcium levels responses to the alpha -adrenergic stimulant, methoxamine [MTX] and the calcium pump inhibitor, cyclopiazonic acid [CPA] were tested on the aorta of streptozotocin [STZ] diabetic rats 2, 8 and 16 weeks after induction of diabetes. Neither MTX-nor CPA-evoked vasoconstrictor responses were changed in the 2-weeks-diabetic rats. In contrast, both MTX and CPA-induced contractions were significantly [P < 0.05] increased in the 8-weeks diabetic tissues. Conversely, the maximal vasoconstrictor responses to both MTX and CPA were significantly [P <0.05] reduced in the 16-weeks diabetic tissues [P < 0.05]. The increased MTX-induced contractions 8-wekks after induction of diabetes, and the reduction of responses in corresponding tissues 16-weeks after diabetes induction were reversed in the presence of the voltage-dependent calcium channel blocker, nifedipine. Changes in MTX-evoked responses in the 16-week diabetic tissues were unaffected in the Ca[++] -free medium or by endothelial denudation. The data of the current study suggest that 1] Contractile responses to MTX and CPA change with the development of diabetes. 2] Middle stages of diabetes may be associated with enhanced contractile responses to the alpha-adrenergic agonists and calcium pump inhibitors, whereas in late stages of diabetes attenuation of responses to the same vasoconstrictor agents may develop, 3] Changes of functional Ca[++] store size in the endoplasmic reticulum, and Ca[++] influx, mainly through voltage-dependent Ca[++] channels, may account for altered contractile responses to MTX and CPA in diabetic rats