Lead-cadmium interaction effect on the responsiveness of rat mesenteric vessels to norepinephrine and angiotensin II.

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 response in all groups. However, the increase in perfusion pressure was greater in rats poisoned with cadmium in comparison to controls. L-NOARG potentiated the A II induced vasoconstriction only in cadmium poisoned rats, also indicating a greater influence of nitric oxide in cadmium treated rat vasculature. Two-way ANOVA showed the existence of lead-cadmium interactions effects on the reactivity of rat isolated mesenteric vessels to NE, A II and papaverine.