Cardiovascular responsiveness to physiological agonists of male rats made hypertensive by long-term exposure to cadmium.

The mechanisms by which cadmium may affect cardiovascular regulation are controversial. In this study, we investigated haemodynamics and cardiovascular reactivity to various physiological agonists in anaesthetized male Sprague-Dawley rats which received, for 190 days, deionized drinking water containing 0 (control), 10 and 20 micrograms/ml of cadmium (as acetate). Systolic and diastolic blood pressure, as well as cardiac inotropism, were increased in a similar manner in the two groups of treated rats. Heart rate was reduced in the rats exposed to the higher dose of cadmium, while no electrocardiographic alteration was demonstrated. Cadmium exposure reduced the pressor responses following intravenous norepinephrine (0.25-1 microgram/kg), angiotensin I (0.25-1 microgram/kg) and higher doses of epinephrine (0.50 and 1 microgram/kg) as well as the depressor responses to bradykinin (0.40-1.6 microgram/kg). On the other hand, the exposed rats showed an increased vascular responsiveness to the beta-adrenoceptor stimulating effects of lower doses of epinephrine (0.125 and 0.25 microgram/kg). Moreover, the effects on blood pressure, heart rate and cardiac inotropism of graduated doses of intravenous acetylcholine, angiotensin II, histamine and serotonin were unchanged. Cadmium was accumulated in the kidney of the treated rats at levels similar to those found in exposed humans. Renal copper and zinc were also augmented, possibly in relation to the cadmium-induced synthesis of metallothionein, a protein able to bind different metals. On the whole, this study suggests that cadmium affects several neurohumoral mechanisms that regulate cardiovascular function. It is likely that the changes in these mechanisms have additive effects, under a possible influence of genetic and/or environmental variables, in determining cardiovascular alterations.