nitroarginine and Cadmium-Poisoning

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.

Topics: Acetylcholine; Animals; Cadmium Chloride; Cadmium Poisoning; Dose-Response Relationship, Drug; Hypertension; Male; Mesenteric Arteries; Muscle, Smooth, Vascular; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitroarginine; Norepinephrine; Rats; Rats, Inbred BUF; Vasoconstriction; Vasoconstrictor Agents; Vasodilator Agents

The comparison of the reactivity to norepinephrine (NE) and angiotensin II (A II) of isolated mesenteric blood vessels obtained from rats simultaneously poisoned with lead and cadmium to those responses of rats treated singly with lead or cadmium was performed. Male Buffalo rats aged 6-8 weeks were administered intragastrically with lead (35 mg Pb/kg body wt.) and/or cadmium (5 mg Cd/body wt.), once a week for a period of 7 weeks. Control rats were given equimolar amounts of sodium acetate and/or sodium chloride. Changes in mesenteric vascular resistance due to NE and A II injections were measured ex vivo as an increase in perfusion pressure in vessels prepared by McGregor's method. The dose-response curve for NE (0.01-5.0 microg) determined for vessels of rats poisoned simultaneously with lead and cadmium was shifted to the left in comparison to controls (not poisoned rats), similarly to these determined for rats poisoned with lead or cadmium. ED(50) NE pointed out in the control group (0.83+/-0.5 microg) was significantly greater than in metal treated groups (0.44+/-0.09; 0.45+/-0.26 and 0.5+/-0.11 microg in lead, cadmium, lead and cadmium-treated rats, respectively). This study indicated a tachyphylaxis in responses of isolated mesenteric vessels to A II injected in increasing doses, and the weaker, in comparison to controls, response of vessels of rats poisoned with lead and/or cadmium to A II at a dose of 0.4 microg. The decreasing response to A II could result from changes in calcium ions transport through L-type channels in vascular smooth muscle cells, because verapamil (2.0 microM) inhibited the A II-induced vasoconstriction more weakly in rats poisoned with metals than in controls. Inhibitor of prostaglandins synthesis, ketoprofen (200 microg/ml per min.) attenuated the pressor effect of NE in blood vessels obtained from all rats, but this effect was less potent in arteries of cadmium poisoned rats. Ketoprofen also inhibited the vasoconstrictory action of A II in all groups, but this effect was lower in vessels of rats poisoned simultaneously with lead and cadmium. We suggest that the release of vasoactive prostaglandins as a consequence of endothelial angiotensin receptor stimulation changes more under the influence of metals administered to rats simultaneously than under the influence or lead or cadmium administered singly. Treatment with a nitric oxide synthase inhibitor (L-NOARG; 22 microg/ml per min.) potentiated a NE-induced pressor respon

Topics: Analysis of Variance; Angiotensin II; Animals; Cadmium Poisoning; Calcium; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; In Vitro Techniques; Ketoprofen; Lead Poisoning; Male; Mesenteric Arteries; Muscle, Smooth, Vascular; Nitric Oxide; Nitroarginine; Norepinephrine; Papaverine; Potassium Chloride; Rats; Rats, Inbred BUF; Receptors, Angiotensin; Vasoconstriction; Vasoconstrictor Agents; Verapamil