Cardiac responsiveness to beta-adrenergics in rats with leadinduced hypertension

Abstract

There are controversial reports about the exact mechanisms of lead-induced hypertension, but alteration in the responsiveness of cardiovascular system to catecholamines may be involved. In the present study, the effect of exposure to low level of lead acetate on responsiveness of isolated beating heart to ?-adrenergics in male rats was investigated, using Langendorff isolated heart. Animals were randomly divided into 4 groups: control and 4, 8 and 12-week lead-treated groups. Lead-treated groups received 100ppm lead acetate in drinking water. The isolated hearts were perfused with Krebs-Henseleit solution at 37آ°C and pH=7.4 under constant pressure and gassed with 95%O2+5%CO2. The blood pressure of anesthetized animals and chronotropic and inotropic responses of the isolated hearts to ?-adrenergics (isoproterenol and dobutamine) were recorded separately and corresponding dose-response curves were obtained. 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 isoproterenol in only 12-week lead-treated group was significantly increased. The inotropic response to this drug was also significantly increased in both 8-and 12-week lead-treated rats (P<0.05). Similar findings were observed with dobutamine, but the contractile response of the latter agent was greater than the isoproterenol. Our results indicate that low-level of lead increases blood pressure and both chronotropic and inotropic effects of ?-adrenergics. These effects could imply an important role in the pathogenesis of lead-induced hypertension.