Role of angiotensin II in arterial pressure and renal hemodynamics in rats with altered renal development: age- and sex-dependent differences

Abstract

Numerous studies have demonstrated that angiotensin II (ANG II) is involved in hypertension and renal changes occurring as a consequence of an adverse event during renal development. However, it was unknown whether this involvement is sex and age dependent. This study examines whether the increments in arterial pressure (AP) and in the renal sensitivity to ANG II are sex and age dependent in rats with altered renal development. It also evaluates whether the ANG II effects are accompanied by increments in AT(1) receptors and oxidative stress. Experiments were performed in 3- to 4- and 10- to 11-mo-old rats treated with vehicle or an AT(1) receptor antagonist (ARAnp) during the nephrogenic period. ARAnp-treated rats were hypertensive, but an age-dependent rise in AP was only found in males. Three days of treatment with candesartan (7 mg·kg(-1)·day(-1)) led to a fall of AP that was greater (P < 0.05) in male than in female 10- to 11-mo-old ARAnp-treated rats. Oxidated proteins were elevated (P < 0.05), and the decrease in AP elicited by candesartan was reduced (P < 0.05) when these rats are also treated with tempol (18 mg·kg(-1)·day(-1)). Hypertension was not maintained by an elevation of AT(1) receptors in kidneys and mesenteric arteries. The acute renal hemodynamic response to ANG II (30 ng·kg(-1)·min(-1)) was similarly enhanced (P < 0.05) in both sexes of ARAnp-treated rats at 3-4 but not at 10-11 mo of age. Our results suggest that an adverse event during the nephrogenic period induces an ANG II-dependent increment in AP that is aggravated only in males during aging and that oxidative stress but not an increase in AT(1) receptor contributes to the rise in AP. This study also shows that the renal hemodynamic sensitivity to ANG II is transitorily enhanced in both sexes of rats with altered renal development.

How the Kidney Is Impacted by the Perinatal Maternal Environment to Develop Hypertension1

“…An increase in renal markers of oxidative stress are also observed in different animal models of developmental insult [106,108,[116][117][118], including adult offspring exposed to prenatal undernutrition [79,80], placental insufficiency [84], or models that involve suppression of the RAS during early life [8,71,83,123]. Importantly, increased oxidative stress is linked to an elevation in blood pressure in the male rat relative to the female rat [119,122,124], suggesting that oxidative stress may contribute to the sexual dimorphic control of blood pressure and cardiovascular risk induced by a prenatal insult.…”

“…Suppression of the RAS during nephrogenesis may contribute to the increase in oxidative stress in adult life. Blockade of the RAS during the postnatal period of the rat that corresponds to nephrogenesis programs hypertension in the adult rat that is reduced by treatment with tempol [122]. An increase in renal markers of oxidative stress are also observed in different animal models of developmental insult [106,108,[116][117][118], including adult offspring exposed to prenatal undernutrition [79,80], placental insufficiency [84], or models that involve suppression of the RAS during early life [8,71,83,123].…”

“…Despite these promising effects, it is important to emphasize that ACE inhibitors and AT 1 R antagonists are potential teratogenic agents to humans [134,135] and thus, their use is contraindicated during pregnancy. Caveats include the numerous studies demonstrating that the use of RAS inhibitors program adverse effects when administered prenatally in the rat [122,[136][137][138]] as compared to their action when administered after weaning [120,131,133]. Taken together, PAIXÃ O AND ALEXANDER these studies indicate early lifestyle changes including antioxidant supplementation, a balanced diet, salt restriction, or even therapeutic maneuvers can serve as potential targets and may prove effective in counteracting the adverse programming of chronic health in the event that adverse environmental influences during development cannot be avoided.…”

Morphological and functional effects on cardiac tissue induced by moderate zinc deficiency during prenatal and postnatal life in male and female rats

“…Moreover, innate sex differences and epigenetic changes, as well as changes in both gene expression associated with sex chromosomes and the activity of systems modulated by sex hormones, could explain the differences found in our experimental model (25)(26)(27). In these regard, estrogen has been demonstrated to modulate the renin-angiotensin-aldosterone system and to have beneficial effects on cardiovascular function through actions in the kidney, heart, vasculature, and central nervous system (30,36). Moreover, cardiac sex differences induced by zinc deficiency could also be mediated by changes in oxidative stress and in the nitric oxide system.…”

Kidney Disease and Perinatal Programming of Arterial Hypertension: the Results of Experimental Researches

“…Добавление в еду таким крысам антиоксидан-тов уменьшало у них оксидативное повреждение почек и предупреждало развитие АГ у самцов [66]. В этих экспе-риментах установлено, что повреждение оксидативным стрессом почек крыс самцов было более выражено, чем у самок [67].…”