Selective impairment of hindquarters vasodilator responses to bradykinin in conscious Wistar rats with streptozotocin-induced diabetes mellitus.
1. Male, Wistar rats were treated with streptozotocin (STZ, 70 mg kg-1, i.p.) or saline and chronically instrumented with pulsed Doppler probes and intravascular catheters (implanted under sodium methohexitone anaesthesia) to allow assessment of haemodynamics in the conscious state 28 days later. 2. Control and STZ-treated rats received bolus doses of glyceryl trinitrate (10-80 nmol kg-1), acetylcholine (0.1-5 nmol kg-1) and bradykinin (0.3-30 nmol kg-1). 3. Although, as reported previously, STZ-treated rats had normal mean arterial blood pressure together with renal and mesenteric vasodilatations and hindquarters vasoconstriction relative to control rats, both groups showed similar hypotensive and regional haemodynamic responses to glyceryl trinitrate and acetylcholine. However, while the depressor effects of bradykinin were similar in control and STZ-treated rats, the former showed a hindquarters vasodilator response to bradykinin that was absent in the STZ-treated rats. 4. A loss of bradykinin-mediated vasodilatation in the hindquarters vascular bed in STZ-treated rats in the presence of normal, hindquarters vasodilator responses to other agents and normal bradykinin-mediated vasodilator responses in other vascular beds is consistent with existing evidence that the vasodilatation elicited by bradykinin in the hindquarters vascular bed is particularly dependent on nitric oxide synthesis and that this is impaired selectively in STZ-treated rats.
Kiff
R J
RJ
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre.
Gardiner
S M
SM
Compton
A M
AM
Bennett
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000098:blood supply*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D001786:Blood Glucose; D001120:Arginine; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester