Effects of verapamil on the cardiac alpha 1-adrenoceptor signalling system in diabetic rats

Eur J Pharmacol. 1993 Jan 15;244(2):105-9. doi: 10.1016/0922-4106(93)90014-z.

Abstract

We evaluated the effects of chronic verapamil treatment on the cardiac alpha 1-adrenoceptor signalling system in streptozocin-induced diabetic rats. The decrease in maximum cell surface [3H]bunazosin binding (Bmax) in isolated cardiac myocytes from the diabetic group (-46%, P < 0.01) was completely reversed by a 4-week course of verapamil, while Bmax in the verapamil-treated control group was unchanged. Similarly, the reduction in ventricular inositol 1,4,5-trisphosphate (IP3) production after stimulation with 10 microM noradrenaline (NA) seen in diabetes (-30%, P < 0.01) was completely normalized by verapamil, while the response in the verapamil-treated control group was unaffected. These results indicate that verapamil can induce complete recovery of the impaired cardiac alpha 1-adrenoceptor signalling system in the diabetic heart without affecting glucose metabolism.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / physiopathology*
  • Heart / drug effects
  • Heart / physiopathology*
  • Inosine Triphosphate / biosynthesis
  • Insulin / blood
  • Male
  • Myocardium / enzymology
  • Norepinephrine / pharmacology
  • Protein Kinase C / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha / drug effects*
  • Signal Transduction / drug effects*
  • Verapamil / pharmacokinetics
  • Verapamil / pharmacology*

Substances

  • Blood Glucose
  • Insulin
  • Receptors, Adrenergic, alpha
  • Inosine Triphosphate
  • Verapamil
  • Protein Kinase C
  • Norepinephrine