Nifedipine and alpha adrenoceptors in rat aorta. II. Role of extracellular calcium in enhanced alpha-2 adrenoceptor-mediated contraction in diabetes.
The mechanism responsible for increased norepinephrine-induced responsiveness of aortas isolated from streptozotocin-diabetic rats compared to age-matched control animals was investigated. Selective alpha-1 and alpha-2 adrenoceptor agonists and antagonists were used to determine the contribution of these receptor subtypes to the norepinephrine-induced contractile response. Findings from these experiments indicated an enhancement of alpha-2 adrenoceptor-mediated contraction in aortas from diabetic rats, whereas alpha-1-mediated responses were not altered. The contribution of extracellular calcium influx to the agonist-induced contractions was determined by using the calcium entry blocker nifedipine. Contractile responses to maximally effective concentrations of norepinephrine, phenylephrine and clonidine were separated into fast and slow components and the effect of increasing concentrations of nifedipine on the responses was determined. These experiments indicated that the fast component of contraction to alpha adrenoceptor agonists was insensitive to nifedipine treatment, whereas the slow component was inhibited effectively. The slow component of contraction in response to norepinephrine and clonidine in aortas from diabetic rats was increased significantly compared to control tissues. These results suggest that there is an increase in alpha-2 adrenoceptor activity in aortas from diabetic rats. Furthermore, the increased aortic contractile responses induced by norepinephrine and selective alpha-2 agonists are due probably to an increased influx of extracellular calcium through nifedipine-sensitive ion channels associated with activation of alpha-2 adrenoceptors.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D011189:Potassium Chloride; D009543:Nifedipine; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin