Regulation of papillary plasma flow by angiotensin II

Faubert, Pierre F.; Chou, Shyan–Yih; Porush, Jerome G.

doi:10.1038/ki.1987.234

Cited by 89 publications

(44 citation statements)

References 19 publications

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“…AT 1 receptors expressed in the renal vasculature also have important regulatory effects on sodium handling (50). Renal vasoconstriction caused by Ang II, which we have previously shown to be primarily mediated by AT 1A receptors (51), reduces medullary blood flow, blunting the kidney's excretory capacity for sodium (52,53). Our study suggests that the primary mechanism of action of ACE inhibitors and ARBs to reduce blood pressure in hypertensive patients is attenuation of AT 1 receptor signals at one or more of these key sites in the kidney.…”

Section: Discussionmentioning

confidence: 72%

Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney

Crowley

Gurley

Herrera

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

625

542

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Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenged this hypothesis. Based on the critical role of the renin-angiotensin system (RAS) and the type I (AT 1) angiotensin receptor in essential hypertension, we developed an experimental model to separate AT 1 receptor pools in the kidney from those in all other tissues. Although actions of the RAS in a variety of target organs have the potential to promote high blood pressure and end-organ damage, we show here that angiotensin II causes hypertension primarily through effects on AT 1 receptors in the kidney. We find that renal AT1 receptors are absolutely required for the development of angiotensin II-dependent hypertension and cardiac hypertrophy. When AT 1 receptors are eliminated from the kidney, the residual repertoire of systemic, extrarenal AT1 receptors is not sufficient to induce hypertension or cardiac hypertrophy. Our findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications. Further, they suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney. transgenic mice ͉ kidney transplantation ͉ blood pressure H igh blood pressure (BP) is a highly prevalent disorder, and its complications (including heart disease, stroke, and kidney disease) are a major public health problem (1). Despite decades of scrutiny, the precise pathogenesis of essential hypertension has been difficult to delineate. Guyton and his associates suggested that defective handling of sodium by the kidney and consequent dysregulation of body fluid volumes is a requisite, final common pathway in hypertension pathogenesis (2). The powerful capacity of this pathway to modulate blood pressure is illustrated by the elegant studies of Lifton and associates showing that virtually all of the Mendelian disorders with major impact on blood pressure homeostasis are caused by genetic variants affecting salt and water reabsorption by the distal nephron (3). On the other hand, several recent studies have suggested that primary vascular defects may cause hypertension by impacting peripheral resistance without direct involvement of renal excretory functions (4-7).Among the various regulatory systems that impact blood pressure, the RAS has a key role. Inappropriate activation of the RAS, as in renal artery stenosis, leads to profound hypertension and cardiovascular morbidity (8). Moreover, in patients with essential hypertension who typically lack overt signs of RAS activation, ACE inhibitors and angiotensin receptor blockers (ARBs) effectively reduce blood pressure and ameliorate cardiovascular complications (9-11), suggesting that dysregulation of the RAS contributes to their elevated blood pressure.

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Section: Discussionmentioning

confidence: 72%

Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney

Crowley

Gurley

Herrera

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

625

542

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“…MBF has been reported to increase, 20 decrease, 21 or remain unchanged 22 during Ang II infusion to the anesthetized rat. More recently, by using laser-Doppler flowmetry techniques enabling the direct and continuous recording of changes in MBF, Mattson et al 6,7 found that the medullary circulation of anesthetized Sprague-Dawley rats was very refractory to Ang II vasoconstrictor actions.…”

Section: Discussionmentioning

confidence: 99%

Local Renal Medullary L-NAME Infusion Enhances the Effect of Long-Term Angiotensin II Treatment

1999

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Abstract-We hypothesized that the relatively high doses of angiotensin (Ang) II required to produce hypertension in rats were related to stimulation of renal medullary nitric oxide production, which in turn blunted reductions in medullary blood flow and the development of hypertension. Ang II was infused (5 days at 3 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 IV) to uninephrectomized Sprague-Dawley rats in the presence and absence of a continuous medullary interstitial N G -nitro-L-arginine methyl ester (L-NAME) infusion. Renal cortical and medullary blood flows were determined with the use of implanted optical fibers and laser-Doppler flowmetry. Ang II in the absence of medullary nitric oxide synthase inhibition did not change cortical or medullary blood flow or mean arterial pressure. A threshold dose of L-NAME was determined (75 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ) that did not produce significant short-or long-term changes in medullary blood flow and mean arterial pressure. In rats with blunted medullary nitric oxide synthase activity, Ang II infused intravenously resulted in a 30% reduction in medullary blood flow (from 1.3 to 0.9Ϯ0.2V) and Ϸ20 mm Hg increase in mean arterial pressure with Ang II infusion over 5 days. During 70 minutes after the start of intravenous Ang II, there was an immediate reduction in medullary blood flow, with no changes in cortical blood flow or mean arterial pressure. We conclude that the relative insensitivity of rats to long-term elevations of circulating Ang II is due to the potent counterregulatory actions of the nitric oxide system, specifically within the renal medulla. The results provide novel insights of how the organism attempts to protect itself from the hypertensive effects of Ang II. Key Words: hypertension, renal Ⅲ kidney Ⅲ angiotensin II Ⅲ renal blood flow Ⅲ nitric oxide Ⅲ nitric oxide synthase I t is well recognized that elevations of circulating angiotensin (Ang) II cause resetting of the pressure-natriuresis relationship to elevated levels of arterial blood pressure through the renal retention of sodium and volume expansion. 1 Yet considerable species differences have been found in the concentrations of Ang II required to produce chronic hypertension. We have found that Ang II infused long term at concentrations of 3 to 5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 produce Ϸ30 mm Hg increase in mean arterial pressure (MAP) over a period of 1 week in mongrel dogs maintained on a normal daily NaCl diet. 2 Humans exhibit even greater pressor sensitivity to prolonged infusions of Ang II. 3 In contrast, prolonged infusion of Ang II at 3 to 5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1in Sprague-Dawley rats does not lead to a significant increase in MAP, 4 and investigators generally administer Ang II at rates of 30 to 60 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 to induce prolonged hypertension in rats. 5 A number of studies have demonstrated that the medullary vasculature of Sprague-Dawley rats is relatively refractive to the vasoconstrictor effects of Ang II compared with the cortical circulation. 6,7 Subpressor doses of Ang II administered intravenously that can significan...

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“…These results are consistent with several studies that support a physiological role for the RAS in urine concentration. Direct injections of angiotensin II into the renal artery induce increases in urine osmolality (28), and mice that lack the AT 1A receptor produce dilute urine despite a normal renal architecture (29). Several authors have suggested that the renin-angiotensin system is required to produce the low papillary blood flow necessary for maintenance of the normal renal concentration gradient (28,30).…”

Section: Discussionmentioning

confidence: 99%

“…Direct injections of angiotensin II into the renal artery induce increases in urine osmolality (28), and mice that lack the AT 1A receptor produce dilute urine despite a normal renal architecture (29). Several authors have suggested that the renin-angiotensin system is required to produce the low papillary blood flow necessary for maintenance of the normal renal concentration gradient (28,30). However, we cannot yet distinguish between this mechanism and other possibilities, such as hemodynamically mediated reductions in the delivery of solute to the loop of Henle.…”

Section: Discussionmentioning

confidence: 99%

The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice.

Esther¹,

Marino²,

Howard³

et al. 1997

J. Clin. Invest.

268

211

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Angiotensin-converting enzyme (ACE) generates the vasoconstrictor angiotensin II, which plays a critical role in maintenance of blood pressure in mammals. Although significant ACE activity is found in plasma, the majority of the enzyme is bound to tissues such as the vascular endothelium. We used targeted homologous recombination to create mice expressing a form of ACE that lacks the COOH-terminal half of the molecule. This modified ACE protein is catalytically active but entirely secreted from cells. Mice that express only this modified ACE have significant plasma ACE activity but no tissue-bound enzyme. These animals have low blood pressure, renal vascular thickening, and a urine concentrating defect. The phenotype is very similar to that of completely ACE-deficient mice previously reported, except that the renal pathology is less severe. These studies strongly support the concept that the tissue-bound ACE is essential to the control of blood pressure and the structure and function of the kidney. ( J. Clin. Invest. 1997. 99:2375-2385.)

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Regulation of papillary plasma flow by angiotensin II

Cited by 89 publications

References 19 publications

Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney

Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney

Local Renal Medullary L-NAME Infusion Enhances the Effect of Long-Term Angiotensin II Treatment

The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice.

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