Increased renal vascular sensitivity to angiotensin II in hypertension is due to decreased response to prostaglandins

Palmgren, Eva; Widgren, Bengt R.; Aurell, Mattias; Herlitz, Hans

doi:10.1097/00004872-200305000-00022

Cited by 17 publications

(12 citation statements)

References 31 publications

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“…In addition, reduced responsiveness to vasodilator prostaglandins may result in a greater sensitivity to Ang II, at least in the kidney. 53 However, whether the kallikrein-kinin system plays any role in the regulation of basal vascular tone remains open to debate. Under a variety of circumstances, blockade of bradykinin receptors has no or only minimal effects, and it seems quite possible that increased activity of the kallikrein-kinin system stems from its interaction with the renin-angiotensin system.…”

Section: Discussionmentioning

confidence: 99%

The Prothrombotic Paradox of Hypertension

et al. 2005

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Abstract-Despite increased pulsatile stress, thrombotic rather than hemorrhagic events represent a major complication of hypertension. The pathophysiology of thrombosis in hypertension involves the interaction among vascular endothelium and particularly the renin-angiotensin and kallikrein-kinin systems. Because hypertension is often associated with some degree of inflammation, the combination of chronic inflammation and chronic shear stress may convert the normal anticoagulant endothelium into a procoagulant surface, expressing tissue factor. Activation of the renin-angiotensin system leads to activation of nuclear factor B-dependent proinflammatory genes, also accelerating the expression of tissue factor. Renin-angiotensin and kallikrein-kinin systems interact at several levels to modulate coagulation, fibrinolysis, and vasodilatation in such a way that these 2 systems could have a major influence on the occurrence of thrombotic complications. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists may favorably influence the balance between the renin-angiotensin and kallikrein-kinin axis, regulating blood pressure as well as reducing the risk of thrombosis, which may explain part of the clinical efficacy of these drugs. Key Words: renin-angiotensin system Ⅲ kallikrein-kinin systems Ⅲ blood pressure A lthough hypertension exposes blood vessels to increased pulsatile stress, thrombotic rather than hemorrhagic events represent a major complication in hypertensive patients. This apparent contradiction is known as the thrombotic paradox of hypertension or "Birmingham paradox." 1,2 Nevertheless, in hypertension, several thrombogenic abnormalities occur and evidence is emerging that the condition confers a "prothrombotic state." Just as is the case in venous thrombosis, abnormalities in the vessel wall, blood constituents (such as hemostatic and fibrinolytic factors and platelets), and blood flow can precipitate and explain most thrombotic complications. All of the components of this arterial variant of Virchow's triad are dependent on endothelial function. Indeed, vascular endothelium maintains blood fluidity, modulates blood coagulation, promotes or prevents vascular growth, modulates inflammation, and regulates vasomotor tone. 3 The renin-angiotensin and the kallikrein-kinin systems are powerful regulators of these processes. Therefore, in this brief review, we discuss the possible endothelial origin of the prothrombotic state in hypertension in relation to these 2 regulatory systems. As a PubMed search strategy, we selected relevant articles by entering as key words hypertension, renin-angiotensin, aldosterone, kallikrein, (brady)kinin, coagulation, fibrinolysis, and their various combinations.

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Section: Discussionmentioning

confidence: 99%

The Prothrombotic Paradox of Hypertension

et al. 2005

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“…The debate toward the consequence side stems from the observations that endothelial dysfunction is found in all forms of HTN, increases with increases in BP, and is partly reversed by antihypertensive therapy. Other studies have demonstrated that adult SHR have both endothelial dysfunction and overt HTN, while young SHR have endothelial dysfunction but normal BP, suggesting that endothelial dysfunction may be a cause rather than a consequence of HTN (124). Endothelial cell dysfunction involves an imbalance in the release of vasodilatory mediators, such as NO, PGI 2 , and endothelium-derived hyperpolarizing factor (EDHF), and vasoconstrictive mediators, such as ET, ANG II, and thromboxane A 2 (TxA 2 ) (Fig.…”

Section: Renal Endothelial Cell Dysfunction In Htnmentioning

confidence: 98%

“…On the other hand, increased medullary BP or flow induces the renal medullary interstitium and collecting ducts to release PGE 2 . Young humans with a family history of HTN have defective vasodilator prostaglandin system and thereby increased renal vasoconstriction sensitivity to ANG II (124).…”

Section: Renal Endothelial Cell Dysfunction In Htnmentioning

confidence: 99%

Cellular mediators of renal vascular dysfunction in hypertension

Ponnuchamy¹,

Khalil²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Ponnuchamy B, Khalil RA. Cellular mediators of renal vascular dysfunction in hypertension. Am J Physiol Regul Integr Comp Physiol 296: R1001-R1018, 2009. First published February 18, 2009 doi:10.1152/ajpregu.90960.2008.-The renal vasculature plays a major role in the regulation of renal blood flow and the ability of the kidney to control the plasma volume and blood pressure. Renal vascular dysfunction is associated with renal vasoconstriction, decreased renal blood flow, and consequent increase in plasma volume and has been demonstrated in several forms of hypertension (HTN), including genetic and salt-sensitive HTN. Several predisposing factors and cellular mediators have been implicated, but the relationship between their actions on the renal vasculature and the consequent effects on renal tubular function in the setting of HTN is not clearly defined. Gene mutations/ defects in an ion channel, a membrane ion transporter, and/or a regulatory enzyme in the nephron and renal vasculature may be a primary cause of renal vascular dysfunction. Environmental risk factors, such as high dietary salt intake, vascular inflammation, and oxidative stress further promote renal vascular dysfunction. Renal endothelial cell dysfunction is manifested as a decrease in the release of vasodilatory mediators, such as nitric oxide, prostacyclin, and hyperpolarizing factors, and/or an increase in vasoconstrictive mediators, such as endothelin, angiotensin II, and thromboxane A 2. Also, an increase in the amount/activity of intracellular Ca 2ϩ concentration, protein kinase C, Rho kinase, and mitogenactivated protein kinase in vascular smooth muscle promotes renal vasoconstriction. Matrix metalloproteinases and their inhibitors could also modify the composition of the extracellular matrix and lead to renal vascular remodeling. Synergistic interactions between the genetic and environmental risk factors on the cellular mediators of renal vascular dysfunction cause persistent renal vasoconstriction, increased renal vascular resistance, and decreased renal blood flow, and, consequently, lead to a disturbance in the renal control mechanisms of water and electrolyte balance, increased plasma volume, and HTN. Targeting the underlying genetic defects, environmental risk factors, and the aberrant renal vascular mediators involved should provide complementary strategies in the management of HTN. blood pressure; dietary salt; oxidative stress; cytokines; kidney; endothelium; vascular smooth muscle; extracellular matrix; matrix metalloproteinases THE ROLE OF THE KIDNEY IN the regulation of sodium and water balance and blood pressure (BP) is well recognized (53,55,128). A decrease in plasma volume and renal blood flow (RBF) stimulates renin release from the juxtaglomerular cells (JGCs) and activates the renin-angiotensin system (RAS). Renin transforms angiotensinogen to angiotensin I (ANG I), and angiotensin-converting enzyme (ACE) transforms ANG I to ANG II. ANG II stimulates the adrenal cortex to release aldosterone (Aldo), which acts on the rena...

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“…We have shown previously [6] that these individuals also have an enhanced sensitivity in the renal vasculature to low doses of infused Ang II (angiotensin II). In addition, we have recently observed [7] that the renal vascular sensitivity to Ang II in firstdegree relatives of hypertensives is increased due to a defective prostaglandin response.…”

Section: Introductionmentioning

confidence: 99%

Failure of angiotensin II to suppress plasma renin activity in normotensive subjects with a positive family history of hypertension

et al. 2005

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The renin-angiotensin system is implicated in the pathophysiology of hypertension. Renin release is regulated by a number of factors, including circulating Ang II (angiotensin II), the so-called short feedback loop. The aim of the present study was to investigate the responsiveness of circulating Ang II on PRA (plasma renin activity) in normotensive subjects with a PFH or NFH (positive or negative family history of hypertension respectively). PRA, renal haemodynamics and urinary sodium excretion were measured during infusion of Ang II without and with pretreatment with the AT1 (Ang II type 1) receptor blocker irbesartan. Normotensive men with a PFH (n=13) and NFH (n=10), with a mean age of 38 years, were given on different occasions intravenous Ang II infusions of 0.1, 0.5 and 1.0 ng.kg-1 of body weight.min-1 before and after pretreatment with 150 mg of irbesartan once a day for 5 consecutive days. RPF (renal plasma flow) and GFR (glomerular filtration rate) were also measured. Before Ang II infusion, the PFH and NFH groups did not differ with respect to BP (blood pressure), body mass index, PRA, RBF (renal blood flow) or urinary sodium. There was no difference in BP or renal haemodynamic response to the highest Ang II dose between the groups. PRA declined with the highest Ang II dose (P<0.01) in subjects with a NFH, but not in subjects with a PFH. After treatment with irbesartan when Ang II had no effect on BP in either group, Ang II also suppressed PRA in subjects with a PFH (P<0.01), and the difference between the groups at baseline was thus eliminated. In conclusion, these findings indicate that subjects with a PFH have a defective Ang II suppression of PRA, which is corrected by AT1 receptor blockade.

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Increased renal vascular sensitivity to angiotensin II in hypertension is due to decreased response to prostaglandins

Cited by 17 publications

References 31 publications

The Prothrombotic Paradox of Hypertension

The Prothrombotic Paradox of Hypertension

Cellular mediators of renal vascular dysfunction in hypertension

Failure of angiotensin II to suppress plasma renin activity in normotensive subjects with a positive family history of hypertension

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