Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a new model of spontaneous hypertension, namely the Prague hypertensive rat (PHR), hypertension is transferred with a kidney transplanted from the PHR to its normotensive counterpart (PNR) by an as yet unknown mechanism. One candidate may be endothelin (ET), since this potent vasoconstrictor affects vascular tone, renal haemodynamics and renal excretory function, and all members of this peptide family are located within the kidney and act in an autocrine/paracrine fashion. In the present study we investigated, in the renal tissue of PHRs and PNRs: (1) preproET-1 and preproET-3 mRNAs as well as ET-1 and ET-3 peptide distribution, (2) endothelin-converting enzyme (ECE)-1 mRNA expression, and (3) ET receptors and their characteristics in membranes of glomeruli and papillae. In addition, plasma ET concentration and urinary ET excretion were determined. Quantitative measurements by competitive reverse transcription-polymerase chain reaction revealed ET-1 mRNA levels in the renal cortex from PHRs and PNRs of 1.09+/-0.13 and 1. 29+/-0.18 amol/microgram of total RNA respectively, and in red medulla of 2.72+/-0.82 and 3.30+/-0.68 amol/microgram respectively. In contrast, renal papilla from PHRs showed significantly lower levels of preproET-1 mRNA (1.81+/-0.64 amol/microgram of total RNA, compared with 4.25+/-0.82 amol/microgram in PNRs; each n=5; P<0.05). The ET-1 peptide concentration in papillary tissue was also significantly lower in PHRs than in PNRs (120.2+/-30.8 and 491.3+/-53.4 fmol/mg of protein respectively; n=5; P<0.01), whereas it was similar in cortex and medulla from PHRs and PNRs. The preproET-3 mRNA content in renal tissue was much lower than that of preproET-1 mRNA. It was significantly higher in red medulla from PHRs compared with that from PNRs (0.25+/-0.05 and 0.13+/-0.02 amol/microgram of total RNA respectively; P<0.05), but was similar in papillae of PHRs and PNRs (0.04+/-0.02 and 0.05+/-0.01 amol/microgram respectively; n=5). Cortical preproET-3 mRNA was at the lower limit of detection. Similarly, the ET-3 peptide concentration was slightly but significantly higher in the red medulla of PHRs compared with PNRs (15.4+/-2.0 and 8.8+/-0.8 fmol/mg of protein respectively; n=5; P<0. 05), whereas no differences in ET-3 peptide concentration were found in papillae from PHRs and PNRs. ECE-1 mRNA levels were similar in the renal cortex, red medulla and papillae from PHRs and PNRs, ranging between 0.34+/-0.03 and 0.56+/-0.12 amol/microgram of total RNA. Of the total ET receptors in glomerular membranes, 39% were ETA receptors, whereas papillary membranes contained exclusively ETB receptors. PHRs and PNRs showed similar Bmax and Kd values for ET-1 in renal glomerular membranes (Bmax, 6.5+/-1.3 and 4.9+/-1.2 pmol/mg of protein respectively; Kd, 0.69+/-0.10 and 0.56+/-0.10 nM respectively) and papillary membranes (Bmax, 9.7+/-1.1 and 11.3+/-1. 6 pmol/mg of protein respectively; Kd, 0.30+/-0.04 and 0.42+/-0.07 nM respectively). Plasma ET-1/2 concentrations (10.4+/-1.3 and 12. 2+/-1.2 fmol/ml in PHRs and PNRs respectively) and urinary ET-1 excretion (3.1+/-0.3 and 3.0+/-0.2 pmol/24 h in PHRs and PNRs respectively) were similar in hypertensive and normotensive rats. In summary, although tissue levels of preproET-3 mRNA were very low in the kidney, significantly greater amounts of preproET-3 mRNA and ET-3 peptide were found in medullary tissue from PHRs compared with PNRs, a finding that awaits further investigation. In contrast, the preproET-1 mRNA content and ET-1 peptide concentration were significantly lower in papillary tissue from PHRs compared with PNRs. Decreased synthesis of ET-1, which normally antagonizes the action of [Arg8]vasopressin, may allow increased water (and sodium) reabsorption at the level of the inner medullary collecting duct. This intrinsic defect of the kidney in the PHR may contribute to hypertension in this model, and may transmit high blood pressure on transplantation of the 'hypertensive' kidney i
 ...
PMID:The renal endothelin system in the Prague hypertensive rat, a new model of spontaneous hypertension. 1036 99

1. The renal medulla plays an important role in regulating body sodium and fluid balance and blood pressure homeostasis through its unique structural relationships and interactions between renomedullary interstitial cells (RMIC), renal tubules and medullary vasculature. 2. Several endocrine and/or paracrine factors, including angiotensin (Ang)II, endothelin (ET), bradykinin (BK), atrial natriuretic peptide (ANP) and vasopressin (AVP), are implicated in the regulation of renal medullary function and blood pressure by acting on RMIC, tubules and medullary blood vessels. 3. Renomedullary interstitial cells express multiple vasoactive peptide receptors (AT1, ETA, ETB, BK B2, NPRA and NPRB and V1a) in culture and in tissue. 4. In cultured RMIC, AngII, ET, BK, ANP and AVP act on their respective receptors to induce various cellular responses, including contraction, prostaglandin synthesis, cell proliferation and/or extracellular matrix synthesis. 5. Infusion of vasoactive peptides or their antagonists systemically or directly into the medullary interstitium modulates medullary blood flow, sodium excretion and urine osmolarity. 6. Overall, expression of multiple vasoactive peptide receptors in RMIC, which respond to various vasoactive peptides and paracrine factors in vitro and in vivo, supports the hypothesis that RMIC may be an important paracrine target of various vasoactive peptides in the regulation of renal medullary function and long-term blood pressure homeostasis.
 ...
PMID:Renomedullary interstitial cells: a target for endocrine and paracrine actions of vasoactive peptides in the renal medulla. 1087

Endothelin-1 (ET-1) is a pleiotropic hormone produced primarily by the endothelium. Synthesis of ET-1 is stimulated by the major signals of cardiovascular stress, such as vasoactive agents (angiotensin II, norepinephrine, vasopressin, and bradykinin), cytokines (e.g., tumor necrosis factor alpha and transforming growth factor beta), and other factors, including thrombin and mechanical stress. ET-1 induces vasoconstriction, is proinflammatory, promotes fibrosis, and has mitogenic potential, important factors in the regulation of vascular tone, arterial remodeling, and vascular injury. These effects are mediated via two receptor types, ETA and ETB. The role ET-1 plays in normal cardiovascular homeostasis and in mild essential hypertension in humans is unclear. However, certain groups of essential hypertensive patients may have ET-1-dependent hypertension, including blacks (subjects of African descent), salt-sensitive hypertensives, patients with low renin hypertension, and those with obesity and insulin resistance. ET-1 has also been implicated in severe hypertension, heart failure, atherosclerosis, and pulmonary hypertension. In all of these conditions, plasma immunoreactive ET levels are elevated and tissue ET-1 expression is increased. Accordingly, it is becoming increasingly apparent that ET-1 plays an important role in cardiovascular disease and in some forms of hypertension in humans. Data from clinical trials using combined ETA-ETB receptor blockers have already demonstrated significant blood-pressure-lowering effects. Thus, targeting the endothelin system may have important therapeutic potential in the treatment of hypertension, particularly by contributing to the prevention of target organ damage and the management of cardiovascular disease.
 ...
PMID:Role of endothelin in human hypertension. 1283 65

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease that causes kidney failure and accounts for 10% of all patients who are on renal replacement therapy. However, the marked phenotypic variation between patients who carry the same PKD1 or PKD2 mutation suggests that nonallelic factors may have a greater influence on the cystic phenotype. Endothelin-1 (ET-1) transgenic mice have been reported to develop profound renal cystic disease and interstitial fibrosis without hypertension. The hypothesis that ET-1 acts as a modifying factor for cystic disease progression was tested in an orthologous mouse model of ADPKD (Pkd2(WS25/-)). Four experimental groups (n = 8 to 11) were treated from 5 to 16 wk of age with the highly selective orally active receptor antagonists ABT-627 (ETA) and A-192621 (ETB) singly or in combination. Unexpected, ETB blockade led to accelerated cystic kidney disease. Of significance, this was associated with a reduction in urine volume and sodium excretion and increases in urine osmolarity and renal cAMP and ET-1 concentrations. The deleterious effect of chronic ETB blockade was neutralized by simultaneous ETA blockade. ETA blockade alone resulted in a significant increase in tubular cell proliferation but did not alter the cystic phenotype. It is concluded that the balance between ETA and ETB signaling is critical for maintaining tubular structure and function in the cystic kidney. These results implicate ET, acting via vasopressin-dependent and independent pathways, as a major modifying factor for cystic disease progression in human ADPKD.
 ...
PMID:Endothelin B receptor blockade accelerates disease progression in a murine model of autosomal dominant polycystic kidney disease. 1720 12

Endothelin-1 (ET-1) is a powerful vasoconstrictor and mitogen that contributes to blood pressure elevation and related vascular remodeling and target organ damage. ET-1 also influences salt and water homeostasis through effects on the renin-angiotensin-aldosterone system and vasopressin, thus elevating blood pressure and increasing vascular tone. Circulating ET-1 levels are elevated in a variety of animal models of hypertension, particularly those that are salt-dependent, and in a subset of human hypertensives, i.e. African-Americans and those with renal dysfunction. ET type B receptors, which normally have vasodilator functions, mediate vasoconstriction in some hypertensives, and hypertensive African-American patients may have increased numbers of vasoconstrictor ET-B receptors in their vascular smooth muscle. Whether selective ET-A or combined ET-A/ET-B receptor antagonists are more efficacious in treating hypertension and related cardiovascular disease is controversial. ET antagonists have only modest BP lowering effects in the general population of essential hypertensives, but show promise in patients with severe, treatment resistant hypertension.
 ...
PMID:The role of endothelin-1 in human hypertension. 1764 6

It is now becoming clear that two major systems namely the sympathetic nervous system and the renin-angiotensin system are activated in response to ischemic injury; these result in the elevation of plasma catecholamines and angiotensin II during the development of myocardial infarction as well as congestive heart failure. Although plasma levels of several other hormones including aldosterone, endothelin, vasopressin, natriuretic peptides, growth factors and inflammatory cytokines are also increased in heart failure, their relationship with changes in catecholamine and/or angiotensin levels as well as their significance for the induction of congestive heart failure are poorly understood. In this article we have examined the evidence regarding the role of endothelin and vasopressin in the pathogenesis of cardiac hypertrophy and congestive heart failure in addition to evaluating the significance of their antagonism by using their receptor blockade for treatment of congestive heart failure. Endothelin appears to maintain blood pressure by its vasoconstricting action whereas vasopressin primarily produces similar effect by retention of body fluid. Myocardium is also known to express both ET-A and ET-B receptors in addition to V1 and V2 receptors for vasopressin, which have been shown to induce cardiac remodeling. Out of various ET-1 receptor antagonists, which are available, a non-selective endothelin receptor antagonist, bosentan, as well as an ET-A receptor antagonist, BQ-123, seem most promising for the treatment of congestive heart failure. Likewise, vasopressin antagonists such as a non-selective antagonist, conivaptan, as well as V2 selective antagonist, tolvaptan, may prove highly valuable for the therapy of this condition. Since most of the existing interventions are helpful in treating patients with congestive heart failure only partially, there appears to be a real challenge for developing some combination therapy for the treatment of congestive heart failure.
 ...
PMID:Potential of endothelin-1 and vasopressin antagonists for the treatment of congestive heart failure. 1976 21

Low blood concentrations of 25-hydroxyvitamin D(3) are associated with increased mortality, while some studies suggest improved cardiovascular outcomes with vitamin D(3) supplementation in chronic kidney disease. However, the physiological effects of vitamin D(3) on the cardiovascular system remain poorly understood making it difficult to determine whether vitamin D(3) supplementation might provide cardiovascular benefit or even cause harm. Thus here we investigated the effects of chronic 1,25-dihydroxyvitamin D(3) treatment on intracellular signaling in human coronary artery smooth muscle cells (HCASMCs) and found that 1,25-dihydroxyvitamin D(3) significantly potentiated endothelin (ET-1) signaling. Specifically, 1,25-dihydroxyvitamin D(3) (24-h pretreatment) caused a more than threefold enhancement in both ET-1-induced intracellular calcium mobilization and extracellular signal-regulated kinase (ERK) activation. This 1,25-dihydroxyvitamin D(3)-elicited signaling enhancement was not observed for either vasopressin or carbachol. With the use of endothelin receptor (ETR) isoform-selective antagonists, ETRA was found to be primarily responsible for the 1,25-dihydroxyvitamin D(3)-induced ET-1 responsiveness and yet ETRA mRNA expression and protein abundance were unaltered following 1,25-dihydroxyvitamin D(3) treatment. While there was an increase in ETRB mRNA expression in response to 1,25-dihydroxyvitamin D(3), the protein abundance of ETRB was again unchanged. Finally, ETRA/ETRB heterodimerization was not detected in HCASMCs in either the absence or presence of 1,25-dihydroxyvitamin D(3). Together, these data show for the first time that 1,25-dihydroxyvitamin D(3) enhances endothelin responsiveness in HCASMCs and that the effect is mediated through ETRA.
 ...
PMID:Increased endothelin-1 responsiveness in human coronary artery smooth muscle cells exposed to 1,25-dihydroxyvitamin D(3). 2334 60

The content of hyaluronan (HA) in the interstitium of the renal medulla changes in relation to body hydration status. We investigated if hormones of central importance for body fluid homeostasis affect HA production by renomedullary interstitial cells in culture (RMICs). Simultaneous treatment with vasopressin and angiotensin II (Ang II) reduced HA by 69%. No change occurred in the mRNA expressions of hyaluronan synthase 2 (HAS2) or hyaluronidases (Hyals), while Hyal activity in the supernatant increased by 67% and CD44 expression reduced by 42%. The autocoid endothelin (ET-1) at low concentrations (10-10 and 10-8 M) increased HA 3-fold. On the contrary, at a high concentration (10-6 M) ET-1 reduced HA by 47%. The ET-A receptor antagonist BQ123 not only reversed the reducing effect of high ET-1 on HA, but elevated it to the same level as low concentration ET-1, suggesting separate regulating roles for ET-A and ET-B receptors. This was corroborated by the addition of ET-B receptor antagonist BQ788 to low concentration ET-1, which abolished the HA increase. HAS2 and Hyal2 mRNA did not alter, while Hyal1 mRNA was increased at all ET-1 concentrations tested. Hyal activity was elevated the most by high ET-1 concentration, and blockade of ET-A receptors by BQ123 prevented about 30% of this response. The present study demonstrates an important regulatory influence of hormones involved in body fluid balance on HA handling by RMICs, thereby supporting the concept of a dynamic involvement of interstitial HA in renal fluid handling.
 ...
PMID:Hyaluronan Production by Renomedullary Interstitial Cells: Influence of Endothelin, Angiotensin II and Vasopressin. 2923 55


<< Previous 1 2