Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04
  • 2024-05
  • 2024-06
  • 2024-07
  • K02288 sale Long term blood pressure regulation is linked to

    2024-07-09

    Long term blood pressure regulation is linked to renal function through the mechanisms of pressure natriuresis (Evans et al., 2005), which has been shown to be modulated by the RAS (Hall et al., 1999). Key components of the RAS are expressed throughout the kidney, and are implicated in renal excretory and hemodynamic function modulation (Sampson et al., 2012a, Sampson et al., 2012b). AT1 and AT2 Ang II receptors play significant roles in the regulation of renal blood flow. Well-known renal actions of Ang II mediated by the AT1 receptor include afferent and efferent arteriolar vasoconstriction, increased tubular sodium K02288 sale at low doses, inhibition of reabsorption at higher doses, and constriction of renal vessels, which induces changes in renal blood flow, glomerular filtration rate and sodium excretion (Arendshorst et al., 1999, Navar et al., 1996). Furthermore, the AT2 receptor has been reported to be expressed throughout the kidney (Armando et al., 2002, Cao et al., 2000, Miyata et al., 1999), importantly in the afferent arteriole and in the distal tubule, key locations for tubuloglomerular feedback regulation. Ang II, via the AT2 receptor, results in vasodilation of renal afferent arterioles (Arima et al., 1997), which activates the vasodilator/natriuretic cascade resulting in the increased production of bradykinin and nitric oxide. Furthermore, in vitro studies demonstrate that the proximal tubule AT2 receptor is linked not only to inhibition of sodium but also to bicarbonate absorption, an effect that opposes AT1 receptor-mediated responses (Haithcock et al., 1999). In line with this evidence a significant rightward shift in the pressure-natriuresis relationship in AT2 knockout mice has been reported; at similar perfusion pressure AT2 knockout mice excrete 3-fold less sodium and water than wild-type mice (Gross et al., 2000). In the pathophysiology of hypertension, it is clear that the kidneys’ ability to achieve sodium and water homeostasis is compromised and that the set point for pressure-natriuresis is shifted to a higher blood pressure (Hall et al., 1999). Siragy et al. (1999) demonstrated that exogenous administration of Ang II in AT2 knockout mice led to sustained sodium retention and hypertension in contrast to wild-type control mice, highlighting the protective role of AT2 against the antinatriuretic and pressor action of Ang II. Furthermore, ACE inhibitors are clinically effective in the treatment of hypertension and associated end-organ disease (Robles et al., 2014). Ang(1–7) is degraded and inactivated by ACE, and thus the blood pressure-lowering effects of ACE inhibitors and AT1 antagonists may be attributable not only to direct inhibition of Ang II synthesis and direct AT1 receptor blockade, but also to an increase in vasodilator Ang(1–7), all of which produce favorable cardiovascular effects (Brosnihan et al., 1996, Chappell et al., 1998, Li et al., 1997). The pressure-natriuresis relationship is sex-dependent. Studies in normotensive and hypertensive rats have shown that, compared to their male counterparts, females excrete the same amount of sodium as males at a lower arterial pressure and thus show a protective leftward shift in the pressure-natriuresis curve (Hilliard et al., 2011, Khraibi et al., 2001, Reckelhoff et al., 1998). Baiardi et al. (2005) also demonstrated that female renal vasculature show a greater renal AT2 expression. Matching this data, AT2 blockade has been shown to blunt the autoregulation of renal blood flow at low perfusion pressures in females but not in males (Hilliard et al., 2011). The impact of the Mas on renal hemodynamics appears to be sexually dimorphic, since Mas blockade decreases renal blood flow significantly in female but not in male rats (Safari et al., 2012). However, the entire mechanism underlying this sex difference is still unknown. Numerous results demonstrate an activational hormonal effect on RAS components. Studies have shown a greater mRNA expression of AT2, Mas and ACE2 in adult female kidneys than in age-matched males (with a lower AT1/AT2 ratio in females), therefore shifting the balance of the RAS to the vasodilator arm (Baiardi et al., 2005, Hilliard et al., 2013a, Hilliard et al., 2013b, Sampson et al., 2008). Studies in mice demonstrate that females express much higher numbers of renal AT2 receptors than males, and that treatment with estrogen increases renal AT2 receptor expression in male mice (Baiardi et al., 2005). Thus, estrogen treatment can decrease the AT1/AT2 receptor ratio, favoring vasodilation, a shift that may contribute to explain the sex differences in the response to Ang II (Miller et al., 1999, Silbiger and Neugarten, 1995). Furthermore, studies have demonstrated in female wild-type mice that the pressor responsiveness to Ang II was augmented with age and that vehicle-treated aged wild-type mouse had a lower renal AT2R/AT1R balance as compared to adult counterparts (Mirabito et al., 2014).