Sub-chronic lead exposure produces β1-adrenoceptor downregulation decreasing arterial pressure reactivity in rats

- Lead activates sympathetic nervous system with the effect of increased blood pressure and β1-adrenoceptor downregulation.
- Lead exposure activates renin-angiotensin system with the effect of increased blood pressure and heart rate.
- Lead exposure increases cyclooxygenase activity with the effect of increased blood pressure and reduced pressure reactivity.

Lead is considered a causative factor for hypertension and other cardiovascular diseases.AimsTo investigate the effects of sub-chronic lead exposure on blood pressure reactivity and cardiac β1-adrenoceptor activity and to evaluate whether the effects found in vitro are similar to those found in vivo.Main methodsMale Wistar rats were randomly distributed into two groups: control rats (Ct) and rats administered drinking water containing 100 ppm lead (Pb) for 30 days.Key findingsBlood pressure in the Pb rats increased starting from the first week of treatment until the end of the study [systolic blood pressure, Ct: 122 ± 4 vs. Pb: 143 ± 3 mmHg; diastolic blood pressure, Ct: 63 ± 4 vs. Pb: 84 ± 4 mmHg]. The heart rate was also increased (Ct: 299 ± 11 vs. Pb: 365 ± 11 bpm), but the pressure reactivity to phenylephrine was decreased. Losartan and hexamethonium exhibited a greater reduction in blood pressure of Pb rats than in the Ct rats. Isoproterenol increased the left ventricular systolic and end-diastolic pressure, and heart rate only in Ct rats, suggesting that lead induced β1-adrenoceptor downregulation. Indomethacin reduced the blood pressure and heart rate in the Pb rats, suggesting the involvement of cyclooxygenase-derived products (which are associated with reduced nitric oxide bioavailability) in this process.SignificanceThese findings offer further evidence that the effects of sub-chronic lead exposure in vitro can be reproduced in vivo-even at low concentrations-thus triggering mechanisms for the development of hypertension. Therefore, lead should be considered an environmental risk factor for cardiovascular disease.