Enhancement of methoxamine‐induced contractile responses of rat ventricular muscle in streptozotocin‐induced diabetes is associated with α_1A adrenoceptor upregulation

Abstract

These results suggest that impairments of beta-adrenergic and Ca(2+)-handling mechanisms occur early in the development of cardiomyopathy in STZ-induced diabetic rats, and that this is followed by augmentation of alpha(1A) adrenoceptor-mediated inotropy due to alpha(1A) adrenoceptor upregulation.

Mechanisms of α1-adrenoceptor mediated QT prolongation in the diabetic rat heart

“…In 4 week STZtreated diabetic rats in our present study, we also found that it was predominantly the α 1A -AR mRNA and proteins that were up regulated while the α 1B -AR mRNA and protein were not altered in the diabetic rat hearts. However, we found an increase (not decrease, as in the study by Kamata et al, 2006) in the α 1D -AR mRNA in our study, along with undetectable α 1D -AR protein levels. The discrepancy between our study and the previous report (Kamata et al, 2006) on the direction of α 1D -AR change might be due to differences in the duration of the diabetic model (4 weeks vs. 10 weeks of STZ), animal strain (Sprague-Dawley rats vs. Wistar rats) and/or specificity of antibodies used.…”

“…Early study in the 10 week STZinduced diabetic rats showed that α 1A -AR was significantly increased both at the mRNA and protein levels (Kamata et al, 2006). In these diabetic rats, although the α 1D -AR mRNA decreased significantly, the α 1B -AR mRNA was not altered (Kamata et al, 2006).…”

“…Three subtypes of α 1A , α 1B and α 1D -AR were expressed in the control rat hearts (Stewart et al, 1994;Homma et al, 2000) and in diabetic hearts (Kamata et al, 2006). Early study in the 10 week STZinduced diabetic rats showed that α 1A -AR was significantly increased both at the mRNA and protein levels (Kamata et al, 2006).…”

“…Early study in the 10 week STZinduced diabetic rats showed that α 1A -AR was significantly increased both at the mRNA and protein levels (Kamata et al, 2006). In these diabetic rats, although the α 1D -AR mRNA decreased significantly, the α 1B -AR mRNA was not altered (Kamata et al, 2006). In 4 week STZtreated diabetic rats in our present study, we also found that it was predominantly the α 1A -AR mRNA and proteins that were up regulated while the α 1B -AR mRNA and protein were not altered in the diabetic rat hearts.…”

“…Abnormal QT prolongation with the associated arrhythmias is considered a major cardiac electrical disorder and a significant predictor of mortality in diabetic patients (Veglio et al, 2004). Since α 1 -AR has a major compensatory role in regulating cardiac inotropic (Kamata et al, 2006) and chronotropic (McCloskey et al, 2002) effects, especially when β-AR responsiveness is already impaired, we determined the different sensitivities to the α 1 -AR agonist PE in isolated hearts from diabetic and control rats. To determine the ionic mechanisms underlying abnormal α 1 -adrenoceptor mediated QT prolongation in the diabetic rat heart, differential changes of PE on APD at 30% (APD 30 ) and 90% (APD 90 ) depolarization levels, I k , I to and I ss in the left ventricular myocytes from diabetic and control rats were also examined.…”