Temporal alterations in vascular angiotensin receptors and vasomotor responses in offspring of protein-restricted rat dams

Abstract

Objective Examine temporal alterations in vascular angiotensin II (ANG II) receptors (AT1R and AT2R) and determine vascular response to ANG II in growth-restricted offspring. Study design Offspring of pregnant rats fed low-protein (6%) and control (20%) diet were compared. Results Prenatal protein restriction reprogrammed AT1aR mRNA expression in males’ mesenteric arteries to cause 1.7- and 2.3-fold increases at 3 and 6 months of age associated with arterial pressure increases of 10 and 33 mmHg, respectively; however, in females, increased AT1aR expression (2-fold) and arterial pressure (15 mmHg) occurred only at 6 months. Prenatal protein restriction did not affect AT2R expression. Losartan abolished hypertension, suggesting that AT1aR plays a primary role in arterial pressure elevation. Vasoconstriction to ANG II was exaggerated in all protein-restricted offspring, with greater potency and efficacy in males. Conclusion Prenatal protein restriction increased vascular AT1R expression and vasoconstriction to ANG II, possibly contributing to programmed hypertension.

Effects of Oxidative Stress on Vascular Reactivity in the Offspring of Protein-Restricted Stroke-Prone Spontaneously Hypertensive Rats

“…We also found that AChinduced relaxation, but not PE-induced contraction, was lower in the PR group. Similar results have beene reported by Torrens et al, 18) although Sathishkumar et al 19) have reported that prenatal protein restriction increased the expression of the vascular angiotensin II type 1 receptor and the angiotensin II-induced vasoconstriction. These results indicate that a protein restriction in pregnant rats affected the vascular reactivity of their offspring.…”

Enhanced Mesenteric Arterial Responsiveness to Angiotensin II Is Androgen Receptor-Dependent in Prenatally Protein-Restricted Adult Female Rat Offspring1

“…Agtr1b was undetectable in the rat mesenteric arteries, which is similar to the finding in previous studies [7,25]. The mesenteric vascular expression of Agtr1a mRNA was 2-fold higher in proteinrestricted rats compared to control (n ¼ 6 in each group, P , 0.05; Fig.…”

“…Consistent with previous reports [6,10], prenatal protein-restricted adult females have increased plasma testosterone levels. This increased testosterone levels in protein-restricted females is of both ovarian and extraovarian origin and is associated with increased blood pressure [3,[5][6][7] similar to that observed in this study. As reported previously by our group [3] and now confirmed by direct carotid artery catheter, blood pressure was significantly reversed by antiandrogen flutamide, suggesting that hypertension in adult protein-restricted females is androgen receptor dependent.…”

“…A critical role for the RAS is indicated in models of developmental programming of hypertension [7,[21][22][23], and we showed that exaggerated vasomotor responses to Ang II [7] may serve as a potential mechanism. Therefore, the aim of this study was to determine whether the enhanced responsiveness to Ang II and hypertension observed in adult female proteinrestricted rats is testosterone dependent.…”

“…Using a model of protein restriction during rat pregnancy, our laboratory has begun to elucidate the mechanisms linking intrauterine growth restriction and adult life blood pressure [3,[5][6][7]. We previously reported that female growth-restricted offspring from protein-restricted dams exhibit a marked increase in arterial pressure in adulthood that is associated with an increase in expression of mesenteric arterial angiotensin (Ang II) receptor, Agtr1a [7], suggesting that inappropriate activation of the systemic renin-angiotensin system (RAS) is observed in hypertensive adult female protein-restricted offspring. Moreover, blockade of the RAS abolishes hypertension in adult prenatal protein-restricted offspring [7], suggesting that the RAS contributes to the etiology of hypertension in female protein-restricted offspring; yet, the exact mechanism by which the RAS contributes to hypertension in this model is not clear.…”