LEAD-INDUCED HYPERTENSION - POSSIBLE ROLE OF ENDOTHELIAL FACTORS

The results of this study confirm that low lead (0.01%) but not high l ead (0.5%) administration results in increased blood pressure in rats treated for up to 12 months. This effect appeared to be related to an imbalance of endothelially-derived vasoconstrictor and vasodilator com pounds in low lead-treated animals but not in high lead-treated animal s. In low lead-treated rats, measurement of plasma endothelins 1 and 3 (ET-1 and ET-3) revealed that ET-3 concentration increased significan tly after both 3 months (Experimental, 92.1 +/- 9.7 v Control, 46.7 +/ - 12.0 pmol/mL; P < .001) and 12 months (Experimental, 105.0 +/- 9.3 v Control, 94.1 +/- 5.0 pmol/mL; P <.01) while ET-1 was unaffected. Pla sma and urinary cGMP concentrations (as a reflection of endothelium-de rived relaxing factor (EDRF)) decreased significantly at 3 months (pla sma, Experimental, 1.8 +/- 0.9 v Control, 4.2 +/- 1.6 pmol/mL; P <.001 ) and 12 months (plasma, Experimental, 2.2 +/- 0.7 v Control, 4.2 +/- 0.9 pmol/mL; P < .001). Thus, the path to development of hypertension in low lead rats may be through an increase in the concentration of th e vasoconstrictor hormone, ET-3, and a decrease in the vasodilator hor mone, EDRF. High levels of lead exposure did not result in hypertensio n, perhaps because plasma concentrations of ET-1, ET-3 and cGMP were u naltered at 3 months, while ET-1, ET-3 and cGMP concentrations were co ordinately and significantly decreased at 12 months.