Intrauterine undernutrition - renal and vascular origin of hypertension

A large number of clinical and experimental studies supports the hypothesis that intrauterine undernutrition is an important determinant of hypertension, coronary heart disease and non-insulin-dependent diabetes in the adult offspring. in this review, the renal and vascular repercussions of maternal undernutrition are emphasized, and the physiopatologic mechanisms discussed. the origin of hypertension is detailed based upon the findings of kidney functional parameters and endothelium function studies. A working model linking hypertension to intrauterine undernutrition is proposed. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.Univ São Paulo, ICB 1, Dept Farmacol, Lab Hipertensao, BR-05508900 São Paulo, SP, BrazilUniversidade Federal de São Paulo, São Paulo, SP, BrazilUniversidade Federal de São Paulo, São Paulo, SP, BrazilWeb of Scienc

Role of PGI(2) and effects of ACE inhibition on the bradykinin potentiation by angiotensin-(1-7) in resistance vessels of SHR

The present study determined the participation of PGI(2) in the angiotensin-(1-7) [Ang-(1-7)libradykinin (BK) interaction, in the presence and absence of Angiotensin Converting Enzyme (ACE) inhibition, trying to correlate it with tissue levels of both peptides. the isolated mesenteric arteriolar bed of Spontaneously Hypertensive Rats (SHR) was perfused with Krebs or Krebs plus enalaprilat (10 DM), and drugs were injected alone or in association. BK (10 nM)-induced relaxation was potentiated by Ang-(1-7) (2.2 mug) in the presence or absence of enalaprilat. Ang-(1-7) receptor blockade [A-779 (4.8 mug)] did not interfere with the BK effect in preparations perfused with normal Krebs, but reversed the increased BK relaxation observed after ACE inhibition. PGI(2) release by mesenteric vessels was not altered by BK or Ang-(1-7) alone, but was increased when both peptides were injected in association, in the absence or in the presence of enalaprilat. ACE inhibition caused a 2-fold increase in the BK tissue levels, and a significant decrease in the Ang-(1-7) values. We conclude that endogenous Ang-(1-7) has an important contribution to the effect of ACE inhibitors participating in the enhancement of BK response. the mechanism of Ang-(1-7) potentiating effect probably involves an increased production of PGI(2). Our results suggest that a different enzymatic pathway (non-related to ACE) is involved in the local Ang-(1-7) metabolism. (C) 2004 Elsevier B.V. All rights reserved.Univ São Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilUniv Fed Minas Gerais, Inst Biomed Sci, Dept Physiol & Biophys, Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilWeb of Scienc

Role of PGI(2) and effects of ACE inhibition on the bradykinin potentiation by angiotensin-(1-7) in resistance vessels of SHR

The present study determined the participation of PGI(2) in the angiotensin-(1-7) [Ang-(1-7)libradykinin (BK) interaction, in the presence and absence of Angiotensin Converting Enzyme (ACE) inhibition, trying to correlate it with tissue levels of both peptides. the isolated mesenteric arteriolar bed of Spontaneously Hypertensive Rats (SHR) was perfused with Krebs or Krebs plus enalaprilat (10 DM), and drugs were injected alone or in association. BK (10 nM)-induced relaxation was potentiated by Ang-(1-7) (2.2 mug) in the presence or absence of enalaprilat. Ang-(1-7) receptor blockade [A-779 (4.8 mug)] did not interfere with the BK effect in preparations perfused with normal Krebs, but reversed the increased BK relaxation observed after ACE inhibition. PGI(2) release by mesenteric vessels was not altered by BK or Ang-(1-7) alone, but was increased when both peptides were injected in association, in the absence or in the presence of enalaprilat. ACE inhibition caused a 2-fold increase in the BK tissue levels, and a significant decrease in the Ang-(1-7) values. We conclude that endogenous Ang-(1-7) has an important contribution to the effect of ACE inhibitors participating in the enhancement of BK response. the mechanism of Ang-(1-7) potentiating effect probably involves an increased production of PGI(2). Our results suggest that a different enzymatic pathway (non-related to ACE) is involved in the local Ang-(1-7) metabolism. (C) 2004 Elsevier B.V. All rights reserved.Univ São Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilUniv Fed Minas Gerais, Inst Biomed Sci, Dept Physiol & Biophys, Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilWeb of Scienc

Calcium handling by vascular myocytes in hypertension

Calcium ions (Ca2+) trigger the contraction of vascular myocytes and the level of free intracellular Ca2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca2+ plays a role in the augmented vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR) have an increased contractile sensitivity to extracellular Ca2+ and intracellular Ca2+ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca2+ channel density and possibly function in vascular myocytes from hypertensive animals. Several observations using various experimental approaches support this hypothesis: 1) the contractile activity in response to depolarizing stimuli is increased in arteries from hypertensive animals demonstrating increased voltage-dependent Ca2+ channel activity in hypertension; 2) Ca2+ channel agonists such as Bay K 8644 produce contractions in isolated arterial segments from hypertensive rats and minimal contraction in those from normotensive rats; 3) intracellular Ca2+ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca2+ channel agonists and depolarizing interventions, and 4) using the voltage-clamp technique, the inward Ca2+ current in arterial myocytes from hypertensive rats is nearly twice as large as that from myocytes of normotensive rats. We suggest that an alteration in Ca2+ channel function and/or an increase in Ca2+ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertensio

Effects of estrogen on the vascular system

The cardiovascular protective actions of estrogen are partially mediated by a direct effect on the vessel wall. Estrogen is active both on vascular smooth muscle and endothelial cells where functionally competent estrogen receptors have been identified. Estrogen administration promotes vasodilation in humans and in experimental animals, in part by stimulating prostacyclin and nitric oxide synthesis, as well as by decreasing the production of vasoconstrictor agents such as cyclooxygenase-derived products, reactive oxygen species, angiotensin II, and endothelin-1. In vitro, estrogen exerts a direct inhibitory effect on smooth muscle by activating potassium efflux and by inhibiting calcium influx. In addition, estrogen inhibits vascular smooth muscle cell proliferation. In vivo, 17ß-estradiol prevents neointimal thickening after balloon injury and also ameliorates the lesions occurring in atherosclerotic conditions. As is the case for other steroids, the effect of estrogen on the vessel wall has a rapid non-genomic component involving membrane phenomena, such as alteration of membrane ionic permeability and activation of membrane-bound enzymes, as well as the classical genomic effect involving estrogen receptor activation and gene expression