The impact of subchronic cadmium poisoning on the vascular effect of nitric oxide in rats.
The aim of this study was to evaluate the impact of poisoning with cadmium in hypertensive doses (50 or 200 ppm in drinking water for three months) on the basal and stimulated release NO effect in the isolated and perfused rat mesenteric bed. Mesenteric artery preparation preconstricted by norepinephrine (0.5 microg/mL) was used to determine changes in its vascular resistance induced by e-NOS synthase blocker, N-omega-nitro-L-arginine (L-NOARG) injected in increasing doses from 1.0 to 200.0 microg or acetylcholine (ACh) administered in doses from 0.05 x 10(-10) to 5.0 x 10(-10) mol before and during L-NOARG infusion (1.0 microg/mL). Vascular reactivity was measured as an increase or decrease in perfusion pressure in the constant flow system. Rats poisoned with 50 or 200 ppm of cadmium demonstrated a significant decrease (P <0.05) in vascular response to L-NOARG used in doses of 50 or 100 microg. The dose-response curve obtained for L-NOARG was shifted to the right and ED50 value was greater in the group of rats given cadmium in a dose of 200 ppm than in the controls (70.3 +/- 10.7 versus 25.7 +/- 4.8 microg, P <0.01). These rats reacted with lower expressed vasodilatation to ACh in doses to 0.2 x 10(-10) mol. In all poisoned rats, L-NOARG enhanced the effect of ACh used in doses from 0.05 to 0.5 x 10(-10) mol, whereas in the control group this effect was only achieved at 0.1 x 10(-10) mol. The serum nitric oxide concentration was decreased (P <0.05) in both groups of cadmium-treated rats. These results suggest that cadmium in hypertensive doses modifies the vascular effect of NO in basal conditions and after stimulation by ACh.
Skoczynska
A
A
Department of Internal Medicine, Occupational Diseases and Hypertension, Wroclaw Medical University, L Pasteur 4, Wroclaw, Poland. annaskoc@ak.am.wroc.pl
Martynowicz
H
H
D000109:Acetylcholine; D000818:Animals; D019256:Cadmium Chloride / Q000008:administration & dosage; D002105:Cadmium Poisoning / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine; D009638:Norepinephrine; D051381:Rats; D011915:Rats, Inbred BUF; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019256:Cadmium Chloride; D000109:Acetylcholine; D009638:Norepinephrine