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Hypertension. 2008 Apr;51(4):1239-47. doi: 10.1161/HYPERTENSIONAHA.107.106203. Epub 2008 Feb 7.

Prenatal gender-related nicotine exposure increases blood pressure response to angiotensin II in adult offspring.

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Center for Perinatal Biology, Department of Pharmacology and Physiology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.


Epidemiological studies suggest that maternal cigarette smoking is associated with an increased risk of elevated blood pressure (BP) in postnatal life. The present study tested the hypothesis that prenatal nicotine exposure causes an increase in BP response to angiotensin II (Ang II) in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout the gestation. BP and vascular responses to Ang II were measured in 5-month-old adult offspring. Prenatal nicotine had no effect on baseline BP but significantly increased Ang II-stimulated BP in male but not female offspring. The baroreflex sensitivity was significantly decreased in both male and female offspring. Prenatal nicotine significantly increased arterial media thickness in male but not female offspring. In male offspring, nicotine exposure significantly increased Ang II-induced contractions of aortas and mesenteric arteries. These responses were not affected by inhibition of endothelial NO synthase activity. Losartan blocked Ang II-induced contractions in both control and nicotine-treated animals. In contrast, PD123319 had no effect on Ang II-induced contractions in control but inhibited them in nicotine-treated animals. Nicotine significantly increased Ang II type 1 receptor but decreased Ang II type 2 receptor protein levels, resulting in a significant increase in the ratio of Ang II type 1 receptor/Ang II type 2 receptor in the aorta. Furthermore, the increased contractions of mesenteric arteries were mediated by increases in intracellular Ca(2+) concentrations and Ca(2+) sensitivity. These results suggest that prenatal nicotine exposure alters vascular function via changes in Ang II receptor-mediated signaling pathways in adult offspring in a gender-specific manner, which may lead to an increased risk of hypertension in male offspring.

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