Vascular responses of isolated mesenteric resistance and basilar arteries from short- and long-term diabetic rats.
Vascular dysfunctions, e.g. alterations in the reactivity of blood vessels to neurotransmitters and hormones, are a well-established complication of diabetes mellitus. Whether these impairments are a consequence of direct postsynaptic deficits and/or indirect presynaptic deficits remains to be determined. To this end, we investigated the influence of the duration of diabetes on relaxation and contraction responses of isolated mesenteric resistance and equally-sized basilar arteries to postsynaptic activation by various vasoactive agents, using streptozotocin-induced diabetic rats and age-matched controls. Relaxation responses to vasodilator agents were studied in KCl-precontracted arteries. The duration of diabetes (4 or 40 weeks) did not affect the vasodilator responses to sodium nitroprusside or salbutamol in either artery. In mesenteric resistance vessels from short-term (4 weeks) and long-term (40 weeks) diabetic rats the vasoconstrictor responses to KCI, serotonin and vasopressin were the same as those in non-diabetic rats; however, the sensitivity (EC50) to noradrenaline was slightly but significantly enhanced after the long-term diabetic state. In contrast to the mesenteric arteries, noradrenaline did not cause contraction in basilar arteries taken from diabetic and control rats. Thus, there appear to be important differences in the reactivity to noradrenaline of the peripheral and cerebral vasculature. The basilar artery from short-term and long-term diabetic rats did not show different responsiveness to vasopressin whereas to serotonin a significant enhanced and decreased sensitivity (EC10 and EC50) was demonstrated in short-term and long-term diabetes, respectively. Our findings indicate that postsynaptic impairments do not play a major role in the alterations of vasoreactivity to vasodilators, noradrenaline or vasopressin seen in experimental diabetes. However, the duration of the diabetic state may have serious consequences for vasoreactivity of basilar arteries to serotonin and, therefore, warrants further investigations.
Van Buren
T
T
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Medical Faculty, Utrecht University, The Netherlands.
Vleeming
W
W
Krutzen
M M
MM
Van de Kuil
T
T
Gispen
W H
WH
De Wildt
D J
DJ
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D046508:Culture Techniques / Q000379:methods; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013311:Streptozocin