Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Vasopressin V1a and V2 receptors are differentially regulated in deoxycorticosterone acetate-salt hypertension. This paper investigated whether the changes were due to transcription changes in receptor mRNA assessed by in situ hybridization histochemistry (liver V1a receptor) and by reverse transcription-polymerase chain reaction (kidney V1a and V2 receptor). 2. Systolic blood pressure and plasma vasopressin levels were significantly elevated in deoxycorticosterone acetate-salt rats (n = 24) compared with water-control (n = 28) and salt-control rats (n = 28) (P < 0.001). Plasma sodium was elevated in deoxycorticosterone acetate-salt rats compared with both control groups (P < 0.01) and plasma osmolality was elevated in deoxycorticosterone acetate-salt rats compared with water-control rats (P < 0.05). 3. Binding kinetic studies demonstrated downregulation of liver V1a and kidney V2 receptors in deoxycorticosterone acetate-salt rats compared with water-control and salt-control rats (P < 0.05). This was not associated with any change in liver V1a receptor mRNA (P = 0.95), or in kidney V1a (P = 0.79) or V2 receptor mRNA (P = 0.96). 4. In deoxycorticosterone acetate-salt hypertension, downregulation of liver V1a and kidney V2 receptors occurs in the setting of stable vasopressin gene transcription. These results suggest that changes in receptor processing may be responsible for the differential regulation of vasopressin receptors that occurs in deoxycorticosterone acetate-salt hypertension.
 ...
PMID:Vasopressin V1a and V2 receptor mRNA in deoxycorticosterone acetate-salt hypertension in the rat. 968 75

Vasopressin is synthesized by magnocellular neurons in supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei and released by their axon terminals in the neurohypophysis (NH). With its actions as an antidiuretic hormone and vasoactive agent, vasopressin plays a pivotal role in the control of body fluids and cardiovascular homeostasis. Because of its well-defined neurobiology and functional importance, the SON/PVN-NH system is ideal to establish methods for gene transfer of genetic material into specific pathways in the mouse central nervous system. In these studies, we compared the efficiency of transferring the gene lacZ, encoding for beta-galactosidase (beta-gal), versus a gene encoding for green fluorescent protein by using replication-deficient adenovirus (Ad) vectors in adult mice. Transfection with viral concentrations up to 2 x 10(7) plaque-forming units per coverslip of NH, PVN, and SON in dissociated, cultured cells caused efficient transfection without cytotoxicity. However, over an extended period of time, higher levels (50% to 75% of the cells) of beta-gal expression were detected in comparison with green fluorescent protein (5% to 50% of the cells). With the use of a stereotaxic approach, the pituitary glands of mice were injected with Ad (4 x 10(6) plaque-forming units). In material from these animals, we were able to visualize the expression of the beta-gal gene in the NH and in magnocellular neurons of both the PVN and SON. The results of these experiments indicate that Ad-Rous sarcoma virus promoter-beta-gal is taken up by nerve terminals at the injection site (NH) and retrogradely transported to the soma of the neurons projecting to the NH. We conclude that the application of these experimental approaches will provide powerful tools for physiological studies and potential approaches to deliver therapeutic genes to treat diseases.
Hypertension 1999 Oct
PMID:Adenovirus-mediated gene delivery to hypothalamic magnocellular neurons in mice. 1052 56

Vasopressin (AVP) actions on vascular tone and blood pressure are mainly mediated by the V(1)-vascular receptor (V(1)R). We recently reported the structure and functional expression of the human V(1)R cDNA and described the genomic characteristics, tissue expression, chromosomal localization, and regional mapping of the human V(1)R gene, AVPR1A. To test whether the V(1)R is a marker for human essential hypertension, we sequenced the human AVPR1A gene and its 5; upstream region and found several DNA microsatellite motifs. One (GT)(14)-(GA)(13)-(A)(8)microsatellite is located 2983 bp downstream of the transcription start site, within a 2.2 kbp intron interrupting the coding sequence of the receptor. Three other microsatellites are present in the 5; flanking DNA of the AVPR1A gene: a (GT)(25)dinucleotide repeat, a complex (CT)(4)-TT-(CT)(8)-(GT)(24)motif and a (GATA)(14)tetranucleotide repeat located respectively 3956 bp, 3625 bp and 553 bp upstream of the transcription start site. Analysis of these polymorphisms in 79 hypertensive and 86 normotensive subjects for the (GT)(14)-(GA)(13)-(A)(8)and the (GT)(25)motifs revealed a high percentage of heterozygosity but no difference in alleles frequencies between the two groups. A linkage study using the affected sib pair method and the (GT)(25)repeat in 446 hypertensive sib pairs from 282 French Caucasian pedigrees showed no excess of alleles sharing at the AVPR1A locus. No linkage was found in the subgroups of patients with early onset hypertension (diagnosis before age 40) or severe hypertension (diastolic blood pressure >/=100 mmHg or requirement for >/=two medications). These findings suggest that molecular variants of the V(1)R gene are not involved in unselected forms of essential hypertension.
 ...
PMID:Study of V(1)-vascular vasopressin receptor gene microsatellite polymorphisms in human essential hypertension. 1075 13

Vasopressin (AVP) is a cyclic nonapeptide hormone that exhibits many physiological effects including free water reabsorption, vasoconstriction, cellular proliferation and adrenocorticotrophic hormone (ACTH) secretion. In a healthy organism, AVP plays an important role in the homeostasis of fluid osmolality and volume status. However, in several diseases or conditions such as the syndrome of inappropriate secretion of AVP (SIADH), congestive heart failure, arterial hypertension, liver cirrhosis, nephrotic syndrome, dysmenorrhoea and ocular hypertension, AVP may play an important role in their pathophysiology. Recently, orally-active non-peptide AVP receptor antagonists were developed by random screening of chemical entities and optimisation of lead compounds. These include agents specific for the V(1)-vascular and V(2)-renal AVP receptor subtypes. Dual V(1)/V(2) AVP receptor antagonists are also being studied. Some of these non-peptide receptor antagonists have been studied extensively, while others are currently under investigation. Potential therapeutic indications for AVP receptor antagonists comprise: 1) The blockade of V(1)-vascular AVP receptors in arterial hypertension, congestive heart failure, Raynaud's syndrome, peripheral vascular disease and dysmenorrhea. 2) The blockade of V(2)-renal AVP receptors in the syndrome of inappropriate secretion of vasopressin, congestive hart failure, liver cirrhosis, nephrotic syndrome and any state of excessive retention of free water and subsequent dilutional hyponatraemia. 3) The blockade of V(3)-pituitary AVP receptors in ACTH-secreting tumours. This review examines the pharmacology of orally-active non-peptide AVP receptor antagonists and their clinical applications.
 ...
PMID:Development and therapeutic indications of orally-active non-peptide vasopressin receptor antagonists. 1132 60

Vasopressin (VP) and oxytocin (OT), the neurohypophysial hormones of mammals, are generally seen as being involved only in water balance and in parturition and lactation, respectively. In this review, new aspects of their physiology and pathophysiology are explored. Although VP is generally thought of as the antidiuretic hormone (ADH), it also is a highly potent vasoactive peptide. The physiology of VP, both as ADH and as a pressor peptide, is reviewed, and recent evidence suggesting that VP has a role in the maintenance of blood pressure and possibly in the pathogenesis of hypertension is presented. Clinical aspects of diabetes insipidus and of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are reviewed. The importance of identifying cases of SIADH secondary to other pathologies and in which the control of VP secretion is normal is stressed. To distinguish these cases of pseudo-SIADH from those in which the VP secretion control mechanisms respond abnormally, the term SAADH, or syndrome of appropriate secretion of vasopressin, is proposed. The role of OT in lactation and parturition is reviewed. Recent evidence suggesting that the fetus may, at least in part, be responsible for the initiation of labor is presented.
 ...
PMID:The neurohypophysis. 1168 4

Vasopressin is known to acutely stimulate sodium transport in the renal collecting duct. We investigated the long-term regulation by vasopressin of the epithelial sodium channel (ENaC) in the rat kidney. Five-day infusion of dDAVP (a V(2) receptor agonist) to Brattleboro rats lacking vasopressin induced a marked increase in beta- and gamma-subunit ENaC mRNA levels in the renal cortex (beta, 85%; gamma, 100%), with no change in alpha-ENaC mRNA. Expression of beta- and gamma-ENaC mRNAs was also enhanced in lung (beta, 49%; gamma, 33%) but not in distal colon (an organ devoid of V(2) receptors). Similar results were obtained in Sprague Dawley rats after either partial water restriction or dDAVP infusion for 5 days. Transepithelial voltage and transepithelial sodium and water net fluxes were measured in isolated perfused cortical collecting ducts of Brattleboro rats. Acute addition of 2x10(-10) mol/L dDAVP to the bath increased sodium and water fluxes in the same proportion, and to a far greater extent in dDAVP-infused than in control Brattleboro rats (change in Na(+) net flux, 337+/-30 versus 49+/-11 pmol. min(-1). mm(-1), respectively; P<0.001). These effects were abolished by amiloride. Extrarenal water losses, partly originating from the lung, were reduced by high plasma vasopressin level. This study shows that vasopressin increases sodium transport in the renal collecting duct and probably in the lung, through a differential transcriptional regulation of ENaC subunits. This effect is followed by isoosmotic water reabsorption and likely contributes to the process of water conservation. It could lead to less efficient sodium excretion, however, and thus participate in some forms of salt-sensitive hypertension.
Hypertension 2001 Nov
PMID:Chronic exposure to vasopressin upregulates ENaC and sodium transport in the rat renal collecting duct and lung. 1171 12

Vasopressin plays significant role in regulation of blood pressure by means of V1 and V2 receptors, however regulation of synthesis of these receptors in hypertension is only poorly recognized. The purpose of the present study was to compare expression of V1a, V1b and V2 vasopressin (R) mRNA in the renal cortex, renal medulla and the heart of hypertensive renin transgenic TGR(mRen2)27 rats (TGR) and of their parent normotensive Sprague Dawley (SD) strain. The study was performed on 12 weeks old TGR and SD rats. Competitive PCR method was used for quantitative analysis of V1a, V1b and V2 receptors mRNA in fragments of renal cortex, renal medulla and apex of the left ventricle of the heart. In both strains expression of V1aR and V2R mRNA was significantly greater in the renal medulla than in the renal cortex. In the renal medulla but not in the cortex expression of V1aR mRNA was significantly greater in TGR than in SD rats. V2R mRNA expression was similar in the renal cortex and renal medulla of both strains. V1aR mRNA was well expressed in the heart of SD and TGR rats, however there was no significant difference between these two strains. V2R mRNA was not present in the heart. V1bR mRNa could not be detected either in the kidney or in the heart. The results provide evidence for specific increase of expression of V1a receptors mRNA in the renal medulla of TGR rats.
 ...
PMID:Vasopressin V1a, V1b and V2 receptors mRNA in the kidney and heart of the renin transgenic TGR(mRen2)27 and Sprague Dawley rats. 1236 33

We have recently reported that endothelin-1 (ET-1), which is increased in the arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats, stimulates superoxide production. However, the humoral mechanisms responsible for ET-1-induced superoxide formation in low-renin models of hypertension, such as DOCA-salt hypertension, remain undefined. Vasopressin is known to upregulate vascular preproET-1 gene expression in DOCA-salt rats, an effect that is absent in vasopressin-deficient Brattleboro rats treated with DOCA-salt. The present study tested the hypothesis that vasopressin contributes to ET-1-induced vascular superoxide production in DOCA-salt hypertensive rats. Carotid arterial segments of DOCA, sham (uninephrectomized), or normal (untreated) rats were used for the study. In vitro vasopressin treatment of carotid arteries from normal rats for 24 hours, but not 4 hours, increased both ET-1 and superoxide levels. The increase of vasopressin-induced superoxide was reduced by pretreatment of the vessels with ABT627, a selective ETA receptor antagonist ABT627. Vasopressin, ET-1, and superoxide levels were significant elevated in carotid arteries of DOCA-salt rats compared with sham controls. The selective V1-vasopressin receptor antagonist (beta-Mercapto-beta, beta-cyclopentamethylenepropiony1, O-Me-Tyr2, Arg8 vasopressin, ME-AVP), decreased superoxide both in vasopressin-treated vessels of normal rats and in vessels of DOCA-salt rats, with a concomitant reduction of ET-1 content. These results suggest that vasopressin increases vascular superoxide levels by stimulating ET-1 formation in mineralocorticoid hypertension, and that V1-vasopressin receptors play an important role in this process.
Hypertension 2003 Mar
PMID:Vasopressin induces vascular superoxide via endothelin-1 in mineralocorticoid hypertension. 1262 76

Acute electrolytic lesions of the commissural nucleus of the solitary tract (commNTS) reduce blood pressure (BP) in SHR but not in normotensive Wistar-Kyoto and Wistar rats and abolish the pressor response to intravenous injection of potassium cyanide. We investigated the chronic effect of commNTS lesions on mean arterial pressure (MAP), and on baroreceptor and chemoreceptor reflex responses in SHR. The contribution of the sympathetic nervous system and the hormones vasopressin and angiotensin II to maintenance of BP in lesioned SHR was also investigated. MAP fell to normotensive levels the day after lesioning the commNTS but returned to the hypertensive level 9 days later. The reflex tachycardia evoked by sodium nitroprusside remained attenuated for 10 days after commNTS lesions but became enhanced 30 days after commNTS lesions. The pressor component of the chemoreflex elicited by potassium cyanide remained blocked for 30 days after lesions. Vasopressin antagonist or ACE blocker did not change MAP in sham or commNTS-lesioned SHR. Ganglionic blockade with hexamethonium elicited similar reductions in MAP in sham and commNTS-lesioned SHR. Results demonstrated that commNTS lesions in SHR produce a transient fall in BP and a long-lasting inhibition of the pressor response of the chemoreflex. Therefore, the blockade of the pressor response to peripheral chemoreflex activation is not sufficient to chronically reduce MAP in SHR. In the chronic absence of the commNTS, other subnuclei of the NTS or other brain stem nuclei may reorganize to replace the function of commNTS neurons, restoring sympathetic activity and high BP in SHR.
Hypertension 2003 Oct
PMID:Recovery of high blood pressure after chronic lesions of the commissural NTS in SHR. 1290 Apr 28

The Annual Scientific Sessions of the American Heart Association is the leading scientific conference in the cardiovascular field, both for basic and clinical research in cardiology and related disclipines. This report covers the outcome of major clinical trials that were presented in the 'late-breaking' clinical trial sessions. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) investigated the angiotensin receptor blocker valsartan, the angiotensin-converting enzyme inhibitor captopril, and their combination in 14,703 survivors of an acute myocardial infarction with a reduced left ventricular ejection fraction on clinical outcome. The study demonstrated that valsartan and captopril where equally effective, whereas the combination was associated with an increased risk of side effects without further benefit. VALIANT is a landmark trial because it was the first large study that compared the combination of an angiotensin receptor blocker with an angiotensin-converting enzyme inhibitor in the setting of acute myocardial infarction. Other trials that will be summarised in this report are the Na + /H + Exchange Inhibition to Prevent Coronary Events in Acute Cardiac Conditions Trial (EXPEDITION; cariporide in coronary artery bypass graft surgery), the Reversal of Atherosclerosis with Aggressive Lipid Lowering Trial (REVERSAL; atorvastatin and pravastatin for atherosclerosis reversal), the Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation V (SPORTIF V; ximelagatran and warfarin for stroke prevention in atrial fibrillation), the Prophylactic Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularisation (PAPABEAR; amiodarone for the prevention of postoperative atrial fibrillation), the Acute and Chronic Therapeutic Impact of a Vasopressin 2 Antagonist in Congestive Heart Failure (ACTIV in CHF; vasopressin 2 antagonist tolvaptan in congestive heart failure) and Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT; fosinopril and pravastatin in microalbuminuric subjects without hypertension or hypercholesterolemia).
 ...
PMID:American Heart Association scientific sessions. 1510 93


<< Previous 1 2 3 4 5 6 7 8 9 Next >>