Effect of chronic experimental diabetes on vascular smooth muscle function in rabbit carotid artery

Devendra K. Agrawal, Shabir Bhimji, John H. McNeill

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

To understand the effects of diabetes on vascular smooth muscle function and the underlying mechanism(s) involved, we examined the responses to α-adrenoceptor agents, serotonin (5-HT), K+, and prostaglandins in the carotid artery of male New Zealand white rabbits with chronic diabetes (16 weeks) induced chemically by alloxan (100 mg/kg, intravenously) treatment. Isolated ring segments of diabetic rabbit carotid artery exhibited an increased (20-60%) maximal response to norepinephrine (NE), methoxamine, phenylephrine, and K+ as compared with controls. Responses to 5-HT were not significantly increased. Nevertheless, there were no significant differences in ED50 values of the agonists in either of the groups. Putatively selective α2-adrenoceptor agonists (clonidine and guanabenz), prostaglandin E1 (PGE1) and prostaglandin I2 (PGI2) did not elicit any response in control vessels. In the diabetic state, however, these drugs contracted the artery in a dose-dependent fashion. Isoproterenol (0.1-10 μM) relaxed arterial rings previously contracted with all the agonists except PGE1 and PGI2, which were potentiated by isoproterenol. Contractions to PGE1 or PGI2 alone or in the presence of isoproterenol were reduced or abolished by 10-5 M phentol-amine. Under these conditions, isoproterenol exhibited its typical relaxatory action. Nifedipine was more potent in inhibiting the K+ response in diabetic carotid artery than in the controls. These results suggest an increased reactivity of diabetic rabbit carotid artery to (α2-adrenoceptor agonists, K+, PGE1, and PGI2 which may, at least in part, be due to an increased sensitivity of calcium channels in diabetic vessels. Contractile responses to PGE1, and PGI2 could be attributed to their action on adrenergic neurotransmission, thereby facilitating the release of NE from presynaptic nerve terminals. Furthermore, isoproterenol at a high dose (1 μM or more) may directly stimulate α-adrenoceptors. Whether or not this effect of isoproterenol is only prostaglandin-dependent is not clear.

Original languageEnglish
Pages (from-to)584-593
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume9
Issue number5
StatePublished - 1987

Fingerprint

Vascular Smooth Muscle
Isoproterenol
Carotid Arteries
Alprostadil
Epoprostenol
Rabbits
Adrenergic Receptors
Prostaglandins
Serotonin
Norepinephrine
Guanabenz
Serotonin Agents
Methoxamine
Alloxan
Presynaptic Terminals
Clonidine
Phenylephrine
Calcium Channels
Nifedipine
Synaptic Transmission

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Effect of chronic experimental diabetes on vascular smooth muscle function in rabbit carotid artery. / Agrawal, Devendra K.; Bhimji, Shabir; McNeill, John H.

In: Journal of Cardiovascular Pharmacology, Vol. 9, No. 5, 1987, p. 584-593.

Research output: Contribution to journalArticle

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