Mechanism of impaired responses of cerebral arterioles during diabetes mellitus

W. G. Mayhan, L. K. Simmons, G. M. Sharpe

Research output: Contribution to journalArticle

182 Scopus citations

Abstract

The goal of this study was to determine the mechanism of impaired responses of cerebral arterioles during diabetes mellitus. To induce diabetes, rats were injected with streptozotocin. Rats were characterized as diabetic by a blood glucose of >300 mg/dl. Diameter of pial arterioles was mesured with intravital microscopy in nondiabetic and diabetic rats during superfusion with acetylcholine (ACh), ADP, the thromboxane (Tx) analogue U-46619, and nitroglycerin. ACh increased pial arteriolar diameter in nondiabetic rats and did not alter diameter in diabetic rats. ADP increased pial arteriolar diameter in nondiabetic rats and produced minimal changes in diameter of arterioles in diabetic rats. Tx analogue U-46619 produced similar constriction of cerebral arterioles in nondiabetic and diabetic rats. In addition, nitroglycerin produced similar dilatation of cerebral arterioles in nondiabetic and diabetic rats, suggesting that impaired dilatation of cerebral arterioles in diabetic rats was not related to nonspecific impairment of vasodilation. Next, we examined the possibility that impaired responses of cerebral arterioles in diabetic rats in response to ACh and ADP may be related to production of a cyclooxygenase constrictor substance. Indomethacin and the TxA2-prostaglandin (PG) H2 receptor antagonist SQ 29548 restored dilator responses to ACh and ADP in diabetic rats toward that observed in nondiabetic rats. Indomethacin and SQ 29548 did not alter responses in nondiabetic rats. Thus diabetes mellitus impairs endothelium-dependent responses of cerebral arterioles. The mechanism of impaired responses of cerebral arterioles during diabetes mellitus appears to be related to the production of a cyclooxygenase constrictor substance and presumably related to stimulation of the TxA2-PGH2 receptor.

Original languageEnglish (US)
Pages (from-to)H319-H326
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume260
Issue number2 29-2
DOIs
StatePublished - 1991

Keywords

  • Adenosine 5'-diphosphate
  • Indomethacin
  • Microcirculation
  • Nitroglycerin
  • Platelets
  • Rats
  • SQ 29548
  • Stroke Brain
  • Thromboxane

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Mechanism of impaired responses of cerebral arterioles during diabetes mellitus'. Together they form a unique fingerprint.

  • Cite this