Effects of Low Level of Lead Exposure on Responsiveness of The Rat Isolated Heart to Adrenergics

Background: There are controversial reports about the exact mechanisms of lead-induced hypertension, but many factors such as alteration in the responsiveness of cardiovascular system to endogenous substances including catecholamines could be one of the mechanisms involved. In present study, the effect of exposure to 100 ppm lead acetate by drinking water (in the periods of 4, 8 and 12 weeks) on the responsiveness of rat isolated beating heart to β-adrenergics was investigated, using Langendorff isolated heart setup. Methods: The isolated hearts were perfused with Krebs-Henseleit solution at 37˚C and pH=7.4 and gassed with 95% O2 + 5% CO2. The rate (chronotropic) and contractile (inotropic) responses of the heart to β-adrenergics (isoproterenol and dobutamine) were recorded by adding these agents at multiple concentrations to the perfusion solution. Results: The blood pressure in 8- and 12-week lead-treated groups was significantly increased compared with those of the control group (P<0.01). The chronotropic response to many doses of isoproterenol (as β1,2-adrenergic) in only 12-, but not in 4- and 8-week lead-treated groups was significantly increased, as compared with those of control (P<0.05). The inotropic response to this drug was also significantly increased in both 8- and 12-week lead-treated rats (P<0.05, P<0.01). Similar findings were observed in the dobutamine (as selective β1-adrenergic) treated groups, but the contractile response of the latter agent was greater than the isoproterenol. Conclusions: Low-level of lead increases blood pressure and both chronotropic and inotropic effects of β-adrenergics. These effects could imply an important role in the pathogenesis of lead-induced hypertension.