Role of vasopressin in essential hypertension

Bakris, George L.; Bursztyn, Michael; Gavras, Irène; Bresnahan, Margaret; Gavras, Haralambos

doi:10.1097/00004872-199715050-00011

Cited by 99 publications

(51 citation statements)

References 23 publications

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“…16 -19 These observations may be relevant to patients with AD-PKD. AVP secretion is more sensitive to osmotic stimuli, 22 and plasma and/or urinary AVP levels [23][24][25] and urine osmolality 26 are higher in men than in women. Whether men have a higher or a lower renal sensitivity to AVP than women is not clear, because studies on this issue are not in agreement.…”

Section: Resultsmentioning

confidence: 99%

Vasopressin Directly Regulates Cyst Growth in Polycystic Kidney Disease

Wang

Ward

et al. 2008

Journal of the American Society of Nephrology

244

187

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The polycystic kidney diseases (PKD) are a group of genetic disorders causing renal failure and death from infancy to adulthood. Arginine vasopressin (AVP) V2 receptor antagonists inhibit cystogenesis in animal models of cystic kidney diseases, presumably by downregulating cAMP signaling, cell proliferation, and chloride-driven fluid secretion. For confirmation that the protective effect of these drugs is due to antagonism of AVP, PCK (Pkhd1 ), and adolescent nephronophthisis (pcy mouse) by downregulating cAMP signaling, cell proliferation, and chloride-driven fluid secretion. [3][4][5] Clinical trials with V2 receptor antagonists have been initiated. The mechanism by which these drugs inhibit the development of polycystic kidney disease has not been fully elucidated. In addition to V2 antagonism, these drugs could exert an effect by favoring the action of AVP on V1a receptors or by an AVP unrelated mechanism. RESULTS AND DISCUSSIONTo confirm that inhibition of AVP action on the kidney accounts for the effect of V2 receptor antagonists on the development of PKD, we generated PCK AVP ϩ/ϩ , PCK AVP ϩ/Ϫ , and PCK AVP Ϫ/Ϫ rats, as well as wild-type and Brattleboro controls, by breeding F1 rats resulting from PCK (Pkhd1 Ϫ/Ϫ ) and Brattleboro (AVP Ϫ/Ϫ ) crosses. PCK rats are homozygous for a splicing mutation (IVS35-2A3 T)

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Section: Resultsmentioning

confidence: 99%

Vasopressin Directly Regulates Cyst Growth in Polycystic Kidney Disease

Wang

Ward

et al. 2008

Journal of the American Society of Nephrology

244

187

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“…This treatment may be particularly beneficial in hypertensive patients with low renin and high vasopressin plasma levels that are resistant to the usual antihypertensive medication (43).…”

Section: Discussionmentioning

confidence: 99%

Brain renin-angiotensin system blockade by systemically active aminopeptidase A inhibitors: A potential treatment of salt-dependent hypertension

Fournié‐Zaluski

Fassot

Valentin

et al. 2004

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

120

131

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The hyperactivity of the brain renin-angiotensin system (RAS) has been implicated in the development and maintenance of hypertension in several types of experimental and genetic hypertension animal models. We previously reported that in the murine brain, aminopeptidase A (APA) is involved in the conversion of angiotensin II (AngII) to AngIII and that AngIII is one of the main effector peptides of the brain RAS in the control of vasopressin release. Here we report that brain AngIII exerts a tonic stimulatory effect on blood pressure in a model of salt-dependent hypertension, the DOCA-salt rat, characterized by a depressed systemic but a hyperactive brain RAS. Similar high blood pressure accompanied by a low systemic renin state was described in some patients, especially in hypertensive African Americans who are resistant to treatment by blockers of the systemic RAS. We developed RB150, a prodrug of the specific and selective APA inhibitor, EC33. RB150 given i.v. is able to cross the blood-brain barrier, to inhibit brain APA, and to block the formation of central AngIII. A single dose of systemic RB150 (15 mg͞kg, i.v.) in conscious DOCA-salt rats inhibited brain APA activity and markedly reduced blood pressure for up to 24 h. These results demonstrate the crucial role of brain APA as a candidate target for the treatment of hypertension and suggest that RB150, a potent systemically active APA inhibitor, could be the prototype of a new class of antihypertensive agents for the treatment of certain forms of hypertension.

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“…Black hypertensives also tend to exhibit differences in other endocrine characteristics, such as low plasma renin activity, higher levels of endothelin, 17 augmented alpha-adrenergic receptor reactivity, higher levels of plasma vasopressin (AVP) and accentuated hypotensive response to an antivasopressor AVP antagonist. 18 It has also been proposed, but not uniformly accepted, that black subjects have relative insulin resistance. 15 Of particular interest is the fact that some of these racial differences have been observed not only in black hypertensives but also in black normotensives compared to age and gender-matched Caucasians.…”

Section: Hypertension In Black Peoplementioning

confidence: 99%

Genetic epidemiology of essential hypertension

1999

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This review article is intended to introduce the uninitiated clinician to the basic concepts, aims and early findings of the genetic epidemiology of hypertension. It separates the rare monogenic 'Mendelian' hypertensive disorders from the vast majority of patients with essential hypertension, which is a complex, polygenic, multifactorial disorder resulting from interaction of several genes with each other and with the environment. Hypertensive phenotypesEssential hypertension results from the interaction of hereditary and environmental factors and is one of the leading causes of premature cardiovascular morbidity and mortality. Blood pressure levels are highly correlated among family members, a fact attributable to either common genetic background or shared environment and lifestyle habits, or both. Studies of familial aggregation and rates of concordance among monozygotic and dizygotic twins suggest that genes may contribute as much as 40% of the risk to this disorder.1 High blood pressure, defined as systolic pressure у140 mm Hg and diastolic у90 mm Hg, is characterised by a high but variable prevalence rate of 15-25% among populations.2 But blood pressure does not have a bimodal distribution into normal and abnormal groups. Rather, it is a quantitative trait with wide phenotypic variation and a continuous distribution, where an arbitrary cutoff line at some point of the Gaussian curve separates normal from abnormal. This indicates that hypertension is a complex trait, ie, a phenotype that does not follow the classic Mendelian rules of dominant or recessive inheritance attributable to a single gene locus.3 More likely, it is a polygenic and multifactorial disorder, in which

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Role of vasopressin in essential hypertension

Abstract: AVP seems to play a more important role as a pressor hormone in maintaining the elevation of arterial pressure in African-American hypertensives than it does in Caucasian hypertensives.

Cited by 99 publications

References 23 publications

Vasopressin Directly Regulates Cyst Growth in Polycystic Kidney Disease

Vasopressin Directly Regulates Cyst Growth in Polycystic Kidney Disease

Brain renin-angiotensin system blockade by systemically active aminopeptidase A inhibitors: A potential treatment of salt-dependent hypertension

Genetic epidemiology of essential hypertension

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