Lead-induced hypertension: possible role of endothelial factors.
The results of this study confirm that low lead (0.01%) but not high lead (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 compounds in low lead-treated animals but not in high lead-treated animals. In low lead-treated rats, measurement of plasma endothelins 1 and 3 (ET-1 and ET-3) revealed that ET-3 concentration increased significantly 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. Plasma and urinary cGMP concentrations (as a reflection of endothelium-derived relaxing factor (EDRF)) decreased significantly at 3 months (plasma, 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 the vasoconstrictor hormone, ET-3, and a decrease in the vasodilator hormone, EDRF. High levels of lead exposure did not result in hypertension, perhaps because plasma concentrations of ET-1, ET-3 and cGMP were unaltered at 3 months, while ET-1, ET-3 and cGMP concentrations were coordinately and significantly decreased at 12 months.
Khalil-Manesh
F
F
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Gonick
H C
HC
Weiler
E W
EW
Prins
B
B
Weber
M A
MA
Purdy
R E
RE
D000818:Animals; D001158:Arteries / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000502:physiology / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004591:Electrophoresis, Polyacrylamide Gel; D016232:Endothelins / Q000378:metabolism / Q000502:physiology / Q000652:urine; D004730:Endothelium, Vascular / Q000502:physiology*; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007854:Lead / Q000097:blood; D007855:Lead Poisoning / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology / Q000652:urine; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000502:physiology
D016232:Endothelins; D007854:Lead; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D009638:Norepinephrine