title: Enhanced contractile responses of arteries from streptozotocin diabetic rats to sodium fluoride.
abstract: 1. Previous studies from this laboratory have demonstrated that alpha 1-adrenoceptor-mediated increases in tension and phosphoinositide metabolism are enhanced in the aorta and mesenteric arteries from diabetic rats. The purpose of the present investigation was to determine whether contractile responses to sodium fluoride (NaF), which directly stimulates GTP-binding proteins (G-proteins), are also enhanced in diabetic arteries. 2. NaF (1-20 mM) in the presence of 10 microM aluminium chloride produced slowly developing, concentration-dependent contractions in mesenteric arteries from three month streptozotocin-diabetic (60 mg kg-1, i.v.) male Wistar rats and age-matched control rats. The maximum contractile response but not the sensitivity to NaF was significantly greater in mesenteric arteries from diabetic than from control rats, as was the response to noradrenaline (NA). Maximum contractile responses of aorta and caudal artery from diabetic rats to NaF were also significantly enhanced. 3. Removal of the endothelium and denervation with 6-hydroxydopamine did not significantly alter the maximum contractile response of mesenteric arteries from either control or diabetic rats to NaF. Similarly, NaF had no effect on cyclic AMP levels in aorta, and no difference in cyclic AMP levels, either basally or in the presence of NaF, was detected between control and diabetic rat aorta. 4. Contractile responses of mesenteric arteries from both control and diabetic rats to NaF were diminished in calcium-free Krebs solution, but the NaF response remained significantly elevated in mesenteric arteries from diabetic rats compared to control. 5. Ryanodine (30 microM) which depletes intracellular calcium stores, nifedipine (3 microM) which blocks dihydropyridine-sensitive calcium channels and calphostin C (0.5 microM) which selectively inhibits protein kinase C, all significantly inhibited maximum contractile responses of mesenteric arteries from control and diabetic rats to NaF. There were no significant differences between control and diabetic arteries in the relative magnitude of the inhibition produce by the three antagonist. 6. These data suggest that there may be increased activation of the same signalling processes that mediate NA-stimulated vasoconstriction, perhaps contraction-associated G-proteins or the effectors coupled to these G-proteins, in response to NaF in mesenteric arteries from diabetic rats. This may also be responsible for the enhanced contractile responses of these arteries to alpha 1-adrenoceptor stimulation.
authors: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors: L P
authors: LP
authors: Weber
authors: W L
authors: WL
authors: Chow
authors: W
authors: W
authors: Abebe
authors: K M
authors: KM
authors: MacLeod
mesh_terms: D000262:Adenylyl Cyclases / Q000502:physiology; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D019204:GTP-Binding Proteins / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012969:Sodium Fluoride / Q000494:pharmacology*; D013268:Stimulation, Chemical
chemical_list: D017607:Aluminum Compounds; D002121:Calcium Channel Blockers; D002712:Chlorides; D012433:Ryanodine; D000077410:Aluminum Chloride; D012969:Sodium Fluoride; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D009543:Nifedipine; D002118:Calcium