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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the contractile reactivity to various stimuli, and the content and release of noradrenaline (NA) from a non-vascular tissue, the vas deferens, isolated from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The concentration-contraction curves for NA in tissue from animals of two ages (10-25 weeks and 30-45 weeks) were shifted to the left in SHR as compared with in age-matched WKY, with significant differences at 1.0 and/or 10 microM of NA. Similarly, the amplitude of contraction produced by electrical stimulation at 4, 8 and 16 Hz in the tissue was much larger in SHR than in WKY. However, ATP (10-100 microM) evoked contractions of the tissue to a similar extent in both SHR and WKY. The electrically evoked contractions of vas deferens from both strains were inhibited by isoprenaline in an approximate dose-dependent and equipotent manner. The tissue NA content, determined by HPLC-ECD, was nearly same in both SHR and WKY. In addition, the same amount of NA was released from the vas deferens of both strains by electrical stimulation in the presence of 4-aminopyridine. The present findings indicate that the contractile response of vas deferens to stimulation of alpha 1-adrenoceptors, but not of beta-adrenoceptors or P2X-purinoceptors, is more pronounced in SHR than in WKY and that a response indicative of hypertension may also occur in non-vascular tissue as it does in vascular tissue.
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PMID:Hyperreactivity of alpha 1-adrenoceptors, but not of P2X-purinoceptors, in vas deferens of spontaneously hypertensive rats. 165 81

Dual control of local blood flow by purines is described: adenosine 5'-triphosphate (ATP) released as a cotransmitter with noradrenaline from perivascular sympathetic nerves acts on P2X-purinoceptors on smooth muscle cells to produce vasoconstriction; ATP released from endothelial cells during hypoxia (and ADP released from aggregating platelets) acts on P2Y-purinoceptors on endothelial cells which results in production of endothelium-derived relaxing factor and subsequent vasodilatation. It is suggested that the endothelial-mediated vasodilatation is a pathophysiological mechanism to protect the host tissue (e.g. brain or heart) from damage produced by hypoxia following ischaemia. The ATP released from the endothelial cells is rapidly broken down to adenosine which augments this protective mechanism by acting directly on P1-purinoceptors on vascular smooth muscle to produce a longer lasting component of vasodilatation and on perivascular sympathetic nerve terminals to inhibit release of excitatory neurotransmitters. The possibility that impairment of normal endothelial-mediated responses in atherosclerosis and hypertension can lead to local vasospasm is considered.
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PMID:Local control of blood pressure by purines. 303 84

1. Extracellular adenosine triphosphate (ATP) is mitogenic for vascular smooth muscle cells (VSMC) and stimulates several events that are important for cell proliferation: DNA synthesis, protein synthesis, increase of cell number, immediate early genes, cell-cycle progression, and tyrosine phosphorylation. 2. Receptor characterization indicates mitogenic effects of both P2U and P2Y receptors. The P2X receptor is lost in cultured VSMC and is not involved. Several related biological substances such as UTP, ITP, GTP, AP4A, ADP, and UDP are also mitogenic. 3. Signal transduction is mediated via Gq-proteins, phospholipase C beta, phospholipase D, diacyl glycerol, protein kinase C alpha, delta, Raf-1, MEK, and MAPK. 4. ATP acts synergistically with polypeptide growth factors (PDGF, bFGF, IGF-1, EGF, insulin) and growth factors acting via G-protein-coupled receptors (noradrenaline, neuropeptide Y, 5-hydroxytryptamine, angiotensin II, endothelin-1). 5. The mitogenic effects have been demonstrated in rat, porcine, and bovine VSMC and cells from human coronary arteries, aorta, and subcutaneous arteries and veins. 6. The trophic effects on VSMC and the abundant sources for extracellular ATP in the vessel wall make a pathophysiological role probable in the development of atherosclerosis, neointima-formation after angioplasty, and possibly hypertension.
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PMID:Extracellular ATP: a growth factor for vascular smooth muscle cells. 959 70

ATP acts at P2 receptors to contract blood vessels and reactivity to vasoconstrictor agents is often altered in hypertension. This study was designed to identify P2 receptors in mesenteric arteries and veins and to determine whether ATP reactivity is altered in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Computer-assisted video microscopy was used to measure vessel diameter in vitro. ATP was a more potent constrictor of veins (EC(50) = 2.7 microM) than arteries (EC(50) = 196 microM) from normotensive rats; there was no change in ATP reactivity in vessels from DOCA-salt rats. The P2X1 receptor agonist alpha,beta-methylene ATP (alpha,beta-MeATP, 0.03-3 microM) contracted arteries but not veins. ATP-induced contractions in arteries were blocked by alpha,beta-MeATP (3 microM) desensitization. 2-Methylthio-ATP (0.1-10 microM), an agonist that can act at P2Y1 receptors, did not contract arteries or veins, whereas UTP, an agonist at rat P2Y2/P2Y4 receptors, contracted veins (EC(50) = 15 microM) and arteries (EC(50) = 24 microM). UTP-induced contractions of veins cross-desensitized with ATP, whereas UTP-induced contractions in arteries were unaffected by alpha,beta-MeATP-desensitization. The P2X/P2Y1 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4-disulfonic acid blocked ATP-induced contractions of arteries (IC(50) = 4.8 microM) but not veins. Suramin, an antagonist that blocks P2Y2 receptors, partly inhibited ATP- and UTP-induced contractions of veins. Immunohistochemical studies revealed P2X1 receptor immunoreactivity in arteries but not veins. These data indicate that mesenteric vascular reactivity to ATP is not altered in DOCA-salt hypertension. ATP acts at P2X1 and P2Y2 receptors to contract mesenteric arteries and veins, respectively, whereas in arteries UTP acts at an unidentified P2 receptor.
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PMID:Differential localization of P2 receptor subtypes in mesenteric arteries and veins of normotensive and hypertensive rats. 1116 Jun 34

Diadenosine polyphosphates have been characterized as extracellular mediators controlling numerous physiological effects. In this study, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate were isolated and identified in human myocardial tissue. Human myocardial tissue was homogenized and fractionated by affinity chromatography, displacement chromatography, anion-exchange chromatography, and reversed-phase chromatography. In fractions purified to homogeneity, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate were revealed by matrix-assisted laser desorption/ionization mass spectrometry and ultraviolet spectroscopy. These diadenosine polyphosphates were further identified by enzymatic analysis, which demonstrated an interconnection of the phosphate groups with the adenosines in the 5' positions of the riboses. Furthermore, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate were found in human cardiac-specific granules, and the amount of diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate was estimated in the range of approximately 500 micromol/L. In conclusion, the experiments show that the diadenosine polyphosphates with 2 and 3 phosphate groups occur in human myocardial tissue, and so do the diadenosine polyphosphates with 4 to 6 phosphate groups. After being released by cholinergic stimulation, which is known to affect diadenosine polyphosphate release from secretory granules, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate activate P2X purinoceptors in vascular smooth muscle; hence, they can act as vasoconstrictors. It may be inferred that the differential action of both predominantly vasodilator and vasoconstrictor diadenosine polyphosphates allow a fine-tuning of myocardial blood flow by locally released diadenosine polyphosphates.
Hypertension 2004 May
PMID:Endogenous diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate in human myocardial tissue. 1506 58

The contribution of alpha-1 adrenergic receptor (alpha1-AR) subtypes to neurogenic constrictions of mesenteric resistance arteries from SHAM and deoxycorticosterone acetate-salt (DOCA-salt) hypertensive mice was assessed. Frequency-response curves (0.5-30 Hz) for transmural stimulation-evoked contractions were examined in SHAM and DOCA-salt arteries in vitro in the absence (control) and presence of prazosin (0.1 microM), PPADS (10 microM), yohimbine (1 microM), 5-methylurapidil (5-MU; 0.1 microM), L-765,314 (1 microM) and BMY-7378 (0.3 microM); selective antagonists at alpha1-, P2X, alpha2-, alpha1A-, alpha1B-, and alpha1D-AR, respectively. In SHAM arteries, prazosin but not PPADS inhibited neurogenic responses. L-765,314 substantially inhibited neurogenic responses while 5-MU had a small inhibitory effect. BMY-7378 did not alter contractile responses at all. In DOCA-salt arteries, prazosin reduced neurogenic responses with no further significant inhibition seen with PPADS. L-765,314 antagonized neurogenic constrictions to a level similar to that seen in SHAM arteries. Furthermore, 5-MU and BMY-7378 did not affect these responses. The density of noradrenergic nerves (assessed using glyoxylic acid-induced fluorescence) or norepinephrine (NE) content was not altered by DOCA-salt hypertension. These results indicate that NE is the primary mediator of neurogenic constriction of murine mesenteric arteries. Nerve-released NE acts primarily at alpha1B-and to a lesser extent at alpha1A-ARs in SHAM arteries whereas NE mediates neurogenic constrictions in DOCA-salt arteries by acting at alpha1B-ARs.
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PMID:Alpha-1B adrenoceptors mediate neurogenic constriction in mesenteric arteries of normotensive and DOCA-salt hypertensive mice. 1609 79

NO produced by NO synthase (NOS) 3 acts as an autacoid to regulate NaCl absorption in the thick ascending limb. ATP induces NO production by NOS 3 in endothelial cells. We hypothesized that extracellular ATP activates NOS in thick ascending limbs through P2 receptors. To test this, we measured intracellular NO production using the NO-selective fluorescent dye DAF-2 in suspensions of rat medullary thick ascending limbs. We found that ATP increased DAF-2 fluorescence in a concentration-dependent manner, reaching saturation at &200 micromol/L with an EC50 of 37 micromol/L. The increase was blunted by 74% by the nonselective NOS inhibitor L-omega-nitro-arginine-methyl-ester (2 mmol/L; 60+/-7 versus 16+/-6 arbitrary fluorescence units; P<0.02; n=5). In the presence of the P2 receptor antagonist suramin (300 micromol/L), ATP-induced NO production was reduced by 64% (101+/-11 versus 37+/-5 arbitrary fluorescence units; P<0.002; n=5). Blocking ATP hydrolysis with a 5'-ectonucleotidase inhibitor, ARL67156 (30 micromol/L) enhanced the response to ATP and shifted the EC(50) to 0.8 micromol/L. In the presence of ARL67156, the EC50 of the P2X-selective agonist beta,gamma-methylene-adenosine 5'-triphosphate was 4.8 micromol/L and the EC50 for the P2Y-selective agonist UTP was 40.4 micromol/L. The maximal responses for both agonists were similar. Taken together, these data indicate that ATP stimulates NO production in the thick ascending limb primarily through P2X receptor activation and that ATP hydrolysis may regulate NO production.
Hypertension 2006 Mar
PMID:Extracellular ATP stimulates NO production in rat thick ascending limb. 1638 May 39

Obesity is a multifactorial disorder with a complex phenotype. It is a significant risk factor for diabetes and hypertension. We assessed obesity-related traits in a large cohort of twins and performed a genome-wide linkage scan and positional candidate analysis to identify genes that play a role in regulating fat mass and distribution in women. Dizygous female twin pairs from 1,094 pedigrees were studied (mean age 47.0+/-11.5 years (range 18-79 years)). Nonparametric multipoint linkage analyses showed linkage for central fat mass to 12q24 (141 cM) with LOD 2.2 and body mass index to 8q11 (67 cM) with LOD 1.3, supporting previously established linkage data. Novel areas of suggestive linkage were for total fat percentage at 6q12 (LOD 2.4) and for total lean mass at 2q37 (LOD 2.4). Data from follow-up fine mapping in an expanded cohort of 1243 twin pairs reinforced the linkage for central fat mass to 12q24 (LOD 2.6; 143 cM) and narrowed the -1 LOD support interval to 22 cM. In all, 45 single-nucleotide polymorphisms (SNPs) from 26 positional candidate genes within the 12q24 interval were then tested for association in a cohort of 1102 twins. Single-point Monks-Kaplan analysis provided evidence of association between central fat mass and SNPs in two genes - PLA2G1B (P = 0.0067) and P2RX4 (P = 0.017). These data provide replication and refinement of the 12q24 obesity locus and suggest that genes involved in phospholipase and purinoreceptor pathways may regulate fat accumulation and distribution.
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PMID:Linkage and potential association of obesity-related phenotypes with two genes on chromosome 12q24 in a female dizygous twin cohort. 1639 64

Challenges such as hypoxia elicit a powerful response from both the central cardiovascular and respiratory neuronal networks. Recent work indicates that purinergic neurotransmission in the brain stem is an important modulator of central respiratory network responses to hypoxia. This study tests whether alterations in purinergic neurotransmission extend beyond respiratory responses to hypoxia and also mediates respiratory inputs to cardiac vagal neurons. To examine central cardiorespiratory responses to hypoxia, we used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and synaptic neurotransmission to cardioinhibitory vagal neurons. Here we show that P2X receptor activation mediates respiratory-related excitatory neurotransmission to parasympathetic cardiac vagal neurons, the dominant control of heart rate. These data demonstrate a critical functional role for adenosine 5'-triphosphate-mediated purinergic signaling in facilitating respiratory-related excitatory neurotransmission to cardiac vagal neurons after hypoxia.
Hypertension 2007 Jul
PMID:Purinergic P2X receptors mediate excitatory transmission to cardiac vagal neurons in the nucleus ambiguus after hypoxia. 1747 Jul 21

The role of ATP as an extracellular signalling molecule is now well established and evidence is accumulating that ATP and other nucleotides (ADP, UTP and UDP) play important roles in cardiovascular physiology and pathophysiology, acting via P2X (ion channel) and P2Y (G protein-coupled) receptors. In this article we consider the dual role of ATP in regulation of vascular tone, released as a cotransmitter from sympathetic nerves or released in the vascular lumen in response to changes in blood flow and hypoxia. Further, purinergic long-term trophic and inflammatory signalling is described in cell proliferation, differentiation, migration and death in angiogenesis, vascular remodelling, restenosis and atherosclerosis. The effects on haemostasis and cardiac regulation is reviewed. The involvement of ATP in vascular diseases such as thrombosis, hypertension and diabetes will also be discussed, as well as various heart conditions. The purinergic system may be of similar importance as the sympathetic and renin-angiotensin-aldosterone systems in cardiovascular regulation and pathophysiology. The extracellular nucleotides and their cardiovascular P2 receptors are now entering the phase of clinical development.
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PMID:P2 receptors in cardiovascular regulation and disease. 1836 30


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