Mechanism of impaired responses of cerebral arterioles during diabetes mellitus

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

Research output: Contribution to journalArticle

182 Citations (Scopus)

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 TxA 2-prostaglandin (PG) H 2 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 TxA 2-PGH 2 receptor.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume260
Issue number2 29-2
StatePublished - 1991

Fingerprint

Arterioles
Diabetes Mellitus
Adenosine Diphosphate
Acetylcholine
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Thromboxanes
Nitroglycerin
Prostaglandin-Endoperoxide Synthases
Indomethacin
Dilatation
Prostaglandins H
Prostaglandin H2
Streptozocin
Constriction
Vasodilation
Endothelium
Blood Glucose

Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

Mechanism of impaired responses of cerebral arterioles during diabetes mellitus. / Mayhan, William; Simmons, L. K.; Sharpe, G. M.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 260, No. 2 29-2, 1991.

Research output: Contribution to journalArticle

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