The effects of endothelin-1 and NG-nitro-L-arginine methyl ester on regional haemodynamics in conscious rats with streptozotocin-induced diabetes mellitus.
1. Resting haemodynamic status and responses to endothelin-1 (0.0004, 0.04, 0.4 nmol kg-1) and NG-nitro-L-arginine methyl ester (L-NAME, 10 mg kg-1) were assessed in conscious, Wistar rats treated with streptozotocin (STZ) to induce diabetes mellitus, and in control animals treated with saline. 2. In the resting state, STZ-treated rats had a bradycardia relative to control animals (291 +/- 13 and 337 +/- 10 beats min-1, respectively), but mean arterial blood pressures were the same in the two groups (STZ-treated 109 +/- 3; control 114 +/- 4 mmHg). However, the STZ-treated rats had raised renal (105 +/- 9 units) and mesenteric (114 +/- 16 units) vascular conductances and reduced hindquarters vascular conductance (26 +/- 4 units) relative to control rats (renal, 80 +/- 6; mesenteric, 75 +/- 7; hindquarters, 37 +/- 3 units). 3. Increasing doses of endothelin-1 caused similar, early falls and subsequent rises in mean arterial blood pressures in both groups of rats. Although there were initial hindquarters vasodilatations with endothelin-1 that were not different in STZ-treated and control rats, there were subsequent renal and mesenteric vasoconstrictions that were greater in the former. Hence, the similar rises in mean arterial blood pressures must have been accompanied by a greater reduction in cardiac output in the STZ-treated rats. 4. L-NAME caused similar renal and mesenteric vasoconstrictions in control and STZ-treated rats, but there was a smaller pressor effect and an attenuated hindquarters vasoconstrictor response to L-NAME in STZ-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Kiff
R J
RJ
Department of Physiology & Pharmacology, University of Nottingham Medical School, Queen's Medical School.
Gardiner
S M
SM
Compton
A M
AM
Bennett
T
T
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D016232:Endothelins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; 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; D016232:Endothelins; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester