Alteration of the soluble guanylate cyclase system in the vascular wall of lead-induced hypertension in rats.
Low-level lead exposure is a known cause of hypertension that has been associated with increased reactive oxygen species activity and endothelial-dependent vasorelaxation impairment. The effect of lead exposure on the vascular nitric oxide (NO)/cyclic guanocine monophosphate (cGMP) system was analyzed. Wistar rats were exposed to 5 ppm lead acetate in the drinking water during 30 d. Mean arterial BP increased significantly in the lead-treated rats. Relaxation to both acetylcholine and sodium nitroprusside (SNP) was reduced in lead-treated rats; however, the vascular wall of lead-administered rats showed an increased expression of endothelial NO synthase. The expression of both subunits (alpha(1) and beta(1)) of soluble guanylate cyclase (sGC) and the cGMP accumulated in the vascular wall were decreased in lead-treated rats. Cotreatment of lead with vitamin C (3 mmol/L) prevented the increase on mean arterial BP, improved the relaxation to both acetylcholine and sodium nitroprusside, and restored the normal expression of endothelial NO synthase and sGC proteins in the vascular wall. In conclusion, lead exposure altered both the endothelium-dependent and -independent relaxing response and induced a reduced expression of sGC in the vascular wall. These effects were abrogated with the antioxidant vitamin C, which suggests the involvement of reactive oxygen species in the regulation of the NO/cGMP relaxing system in the vascular wall of lead-treated rats.
Marques
María
M
*Cardiovascular and Hypertension Research Laboratory, Fundación Jiménez Díaz, Madrid, Spain; and Department of Nephrology, Hospital Clínico U. San Carlos, Madrid, Spain.
Millás
Inmaculada
I
*Cardiovascular and Hypertension Research Laboratory, Fundación Jiménez Díaz, Madrid, Spain; and Department of Nephrology, Hospital Clínico U. San Carlos, Madrid, Spain.
Jiménez
Ana
A
*Cardiovascular and Hypertension Research Laboratory, Fundación Jiménez Díaz, Madrid, Spain; and Department of Nephrology, Hospital Clínico U. San Carlos, Madrid, Spain.
García-Colis
Elena
E
*Cardiovascular and Hypertension Research Laboratory, Fundación Jiménez Díaz, Madrid, Spain; and Department of Nephrology, Hospital Clínico U. San Carlos, Madrid, Spain.
Rodriguez-Feo
Juan A
JA
*Cardiovascular and Hypertension Research Laboratory, Fundación Jiménez Díaz, Madrid, Spain; and Department of Nephrology, Hospital Clínico U. San Carlos, Madrid, Spain.
Velasco
Sandra
S
*Cardiovascular and Hypertension Research Laboratory, Fundación Jiménez Díaz, Madrid, Spain; and Department of Nephrology, Hospital Clínico U. San Carlos, Madrid, Spain.
Barrientos
Alberto
A
*Cardiovascular and Hypertension Research Laboratory, Fundación Jiménez Díaz, Madrid, Spain; and Department of Nephrology, Hospital Clínico U. San Carlos, Madrid, Spain.
Casado
Santos
S
*Cardiovascular and Hypertension Research Laboratory, Fundación Jiménez Díaz, Madrid, Spain; and Department of Nephrology, Hospital Clínico U. San Carlos, Madrid, Spain.
López-Farré
Antonio
A
*Cardiovascular and Hypertension Research Laboratory, Fundación Jiménez Díaz, Madrid, Spain; and Department of Nephrology, Hospital Clínico U. San Carlos, Madrid, Spain.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000502:physiology; D006162:Guanylate Cyclase / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced* / Q000201:enzymology*; D007854:Lead; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000975:Antioxidants; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D007854:Lead; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D006162:Guanylate Cyclase; D000109:Acetylcholine; D001205:Ascorbic Acid