CEREBROVASCULAR RESPONSIVENESS TO N-G-NITRO-L-ARGININE METHYL-ESTER IN SPONTANEOUSLY DIABETIC RATS

1 There is evidence that endothelial dysfunction is associated with di abetes mellitus. The purpose of the present study was to assess local cerebral blood flow (LCBF) and cerebrovascular responsiveness to the N OS inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) in spontaneous ly diabetic insulin-dependent BioBred (BB) rats. 2 Diabetic rats, and non-diabetic controls, were treated with L-NAME (30 mg kg(-1), i.v.) o r saline, 20 min prior to the measurement of LCBF by the fully quantit ative [C-14]-iodoantipyrine autoradiographic technique. 3 There were n o significant differences in physiological parameters (blood pH, PCO2, and PO2, rectal temperature, arterial blood pressure, or plasma gluco se) between any of the groups of rats, and no difference in either the extent or the temporal characteristics of the hypertensive response t o L-NAME between diabetic and non-diabetic rats. 4 In diabetic rats, a global reduction in basal LCBF was observed, although significant red uctions (between -20 and -30%) were found in only 5 (mainly subcortica l) out of the 13 brain regions measured. Following L-NAME injection, s ignificant reductions in LCBF (between -20 and -40%) were found in the non-diabetic animals. In diabetic animals treated with L-NAME, a sign ificant reduction in LCBF was measured only in the hypothalamus (-33%) . 5 The cerebrovascular response to acute L-NAME is attenuated in spon taneously diabetic insulin-dependent BB rats. This would be consistent with the endothelial dysfunction in cerebral vessels, known to be ass ociated with diabetes mellitus and it is possible that a loss of NO-in duced dilator tone, amongst other factors, may underlie the observed r eductions of basal LCBF in these animals.