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

We compared the phenotype of two common mouse models, C-57BL/6J (C57), which carries only the Ren-1c gene, and 129/SvJ (Sv-129), with both Ren 1d and Ren-2. We hypothesized two renin gene Sv-129 would have increased blood pressure and the renin-angiotensin system would be more influential in regulating renal function compared with one renin gene mice. Sv-129 consistently had higher blood pressure than C-57, whether conscious (128 versus 108 mm Hg, P<0.001) or anesthetized (102 versus 88 mm Hg, P<0.001). Plasma renin concentration in both conscious and anesthetized C-57 mice was 3- to 4-fold higher than in Sv-129 (P<0.05), whereas renal cortical renin content was 2.5-fold higher (P<0.005). Renal blood flow and renal vascular resistance were the same in C-57 and Sv-129. Exogenous angiotensinogen produced identical pressor and renal vasoconstrictor responses in both strains. Blocking AT1 receptors with losartan reduced blood pressure by 19 mm Hg in both strains. Nitric oxide synthase inhibition by l-NAME increased blood pressure by 29 mm Hg in C-57 and 35 mm Hg in Sv-129 mice, but the decrease in renal blood flow was 30% less in C-57 (P<0.025). We conclude that Sv-129 mice with two renin genes have higher blood pressure but lower plasma and renal renin than C-57 mice with one renin gene. Renin substrate may limit angiotensin II production in the mouse. In Sv-129, the influence of nitric oxide on renal but not systemic resistance may be exaggerated. Renin from Ren-2 may act independently of normal renin control mechanisms.
Hypertension 2004 Jan
PMID:Cardiovascular and renal phenotype in mice with one or two renin genes. 1466 50

A 71-year-old man with bilateral renovascular disease was admitted to Hamamatsu University hospital because of appetite loss and acute shortness of breath due to acute pulmonary edema (APE) with accelerated hypertension and renal failure. Hypertension and APE were controlled by an angiotensin converting enzyme inhibitor (ACEI) and four sessions of hemodialysis with reduction of 1.8 kg bodyweight. Renal function was later stabilized and the patient required no ACEI or hemodialysis. A trial of right renal angioplasty 1 month after admission failed and renal function deteriorated (serum creatinine 7.1 mg/dL) with accelerated hypertension, gain of bodyweight and APE. Even after four sessions of hemodialysis with adequate reduction of bodyweight, APE was not controlled, but it rapidly improved after administration of an ACEI, without major bodyweight change. As no apparent cardiac dysfunction was evident, APE might have been caused by a direct action of angiotensin II on hyperpermeability in pulmonary capillaries. Blocking of angiotensin II should be considered in such patients even after introduction of hemodialysis.
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PMID:Rapid improvement of acute pulmonary edema with angiotensin converting enzyme inhibitor under hemodialysis in a patient with renovascular disease. 1525 29

Coronary heart disease and cerebrovascular disease continue to be the leading causes of illness and death among adults from developed countries. Their prevalence is strongly related to the effects of many different risk factors, including high blood pressure, cigarette smoking, dyslipidaemia and diabetes. The management of cardiovascular (CV) risk factors should be viewed as an integrated strategy of intervention aimed at correcting as many of the underlying causes of CV disease as possible. Blocking the renin-angiotensin-aldosterone system with new, well-tolerated antihypertensive drugs, and blood pressure regulation by means of new drugs that also reduce plasma cholesterol levels or improve insulin resistance and glucose tolerance, could lead to a reduction of CV diseases.
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PMID:Novel antihypertensive agents. 1526 36

Periadventitial adipose tissue produces vasoactive substances that influence vascular contraction. Earlier studies addressed this issue in aorta, a vessel that does not contribute to peripheral vascular resistance. We tested the hypothesis that periadventitial adipose tissue modulates contraction of smaller arteries more relevant to blood pressure regulation. We studied mesenteric artery rings surrounded by periadventitial adipose tissue from adult male Sprague-Dawley rats. The contractile response to serotonin, phenylephrine, and endothelin I was markedly reduced in intact vessels compared with vessels without periadventitial fat. The contractile response to U46619 or depolarizing high K+-containing solutions (60 mmol/L) was similar in vessels with and without periadventitial fat. The K+ channel opener cromakalim induced relaxation of vessels precontracted by serotonin but not by U46619 or high K+-containing solutions (60 mmol/L), suggesting that K+ channels are involved. The intracellular membrane potential of smooth muscle cells was more hyperpolarized in intact vessels than in vessels without periadventitial fat. Both the anticontractile effect and membrane hyperpolarization of periadventitial fat were abolished by inhibition of delayed-rectifier K+ (K(v)) channels with 4-aminopyridine (2 mmol/L) or 3,4-diaminopyridine (1 mmol/L). Blocking other K+ channels with glibenclamide (3 micromol/L), apamin (1 micromol/L), iberiotoxin (100 nmol/L), tetraethylammonium ions (1 mmol/L), tetrapentylammonium ions (10 micromol/L), or Ba2+ (3 micromol/L) had no effect. Longitudinal removal of half the perivascular tissue reduced the anticontractile effect of fat by almost 50%, whereas removal of the endothelium had no effect. We suggest that visceral periadventitial adipose tissue controls mesenteric arterial tone by inducing vasorelaxation via K(v) channel activation in vascular smooth muscle cells.
Hypertension 2004 Sep
PMID:Visceral periadventitial adipose tissue regulates arterial tone of mesenteric arteries. 1528 65

Hypertension and noninsulin-dependent diabetes mellitus are usually associated with marked glucose intolerance. Hypertensive and even nonhypertensive diabetic individuals display disturbances of the normal circadian blood pressure rhythm. However, little is known about circadian changes of the glucose uptake in muscle and fat cells, the major glucose utilizing tissues. Therefore, we investigated circadian rhythms of glucose uptake in primary muscle and fat cell cultures of hypertensive and type II diabetic rats and their respective control strains. 2-Deoxy-D-(1-3H)glucose uptake was measured over 48 h after synchronization of cells by means of medium change with and without addition of insulin, phloretine, and/or staurosporine. The circadian changes of glucose uptake were assessed by fitting cosine curves to the uptake values. Insulin stimulation of deoxyglucose uptake was only present in control animals, not in hypertensive and diabetic rats. Deoxyglucose uptake displayed a circadian rhythm in control animals, and was markedly disturbed in hypertensive and diabetic animals. Blocking of glucose transporters by phloretine abolished the circadian pattern of deoxyglucose uptake indicating a role of glucose transporters in its generation. Inhibition of kinases by staurosporine inhibited the insulin-stimulated deoxyglucose uptake, but did not dampen the circadian rhythmicity of basal deoxyglucose uptake. The generation of the circadian rhythm of glucose uptake in muscle and fat cell cultures is therefore probably insulin independent and independent of protein kinases. In summary, our results show for the first time: (a) a circadian rhythm of deoxyglucose uptake in glucose utilizing muscle and fat cells in vitro, (b) a disruption of this rhythm in cells of hypertensive and diabetic rats.
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PMID:Circadian rhythm of glucose uptake in cultures of skeletal muscle cells and adipocytes in Wistar-Kyoto, Wistar, Goto-Kakizaki, and spontaneously hypertensive rats. 1547 Sep 52

Drugs currently known as calcium channel blockers (CCB) were initially called calcium antagonists because of their ability to inhibit calcium-evoked contractions in depolarized smooth muscles. Blocking the entry of calcium reduces the active tone of vascular smooth muscle and produces vasodilatation. This pharmacological property has been the basis for the use of CCBs in the management of hypertension and coronary heart disease. A major question is whether drugs reducing blood pressure have other effects that help prevent the main complications of hypertension, such as atherosclerosis, stroke, peripheral arterial disease, heart failure and end-state renal disease. Experimental studies that focus on this question are reviewed in the present paper.
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PMID:Antioxidant effects and the therapeutic mode of action of calcium channel blockers in hypertension and atherosclerosis. 1632 96

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

Radiation-induced renal injury is characterized by proteinuria, hypertension, and progressive decline in renal function. We have previously shown that in vivo or in vitro irradiation of glomeruli with a single dose of radiation (9.5 Gy) increases glomerular albumin permeability (P(alb)) within 1 hr. The current studies tested the hypothesis that this early radiation-induced increase in P(alb) is caused by the release of arachidonic acid and by the generation of specific arachidonic acid metabolites. Glomeruli obtained from WAG/Rij/MCW rats and cultured rat glomerular epithelial and mesangial cells were studied after irradiation (9.5 Gy, single dose). Arachidonic acid release and eicosanoid synthesis by glomeruli or cultured glomerular cells were measured after irradiation, and the effect of inhibitors of phospholipase A2 (PLA2) and cyclooxygenase (COX) on the irradiation-induced increase in P(alb) was assessed. Arachidonic acid release was demonstrated within 10 mins of irradiation of isolated glomeruli and monolayer cultures of glomerular epithelial and mesangial cells. Prostaglandin F(2alpha) (PGF(2alpha)) and PGE2 release was increased after irradiation of isolated glomeruli. Blocking arachidonic acid release or COX activity before irradiation completely prevented the increase in P(alb). COX inhibition immediately after irradiation also diminished the radiation-induced increase in P(alb). We conclude that arachidonic acid and its COX metabolites play an essential role in the early cellular changes that lead to the radiation-induced increase in P(alb). Understanding of the early epigenetic effects of irradiation may lead to new intervention strategies against radiation-induced injury of normal tissues.
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PMID:Arachidonic acid metabolites mediate the radiation-induced increase in glomerular albumin permeability. 1638 Jun 50

Agonists active at I1-imidazoline receptors (I1R) not only lower blood pressure but also ameliorate glucose intolerance, insulin resistance, and hyperlipidemia with long-term treatment. We sought to determine the possible mechanism for the lipid-lowering actions of imidazolines in a model of metabolic Syndrome X, the spontaneously-hypertensive obese (SHROB) rat. The acute actions of moxonidine and rilmenidine, selective I1R agonists, were compared to a specific alpha2-adrenergic receptor agonist, guanabenz, with and without selective receptor blockers. Moxonidine and rilmenidine rapidly reduced plasma triglyceride (20+/-4% and 21+/-5%, respectively) and cholesterol (29+/-9% and 27+/-9%). In contrast, the specific alpha2-adrenergic receptor agonist guanabenz failed to reduce plasma lipids. Blocking experiments showed that moxonidine's actions were mediated by I1R and not alpha2-adrenergic receptors. To evaluate a hepatic site of action, radioligand binding studies with liver plasma membranes confirmed the presence of I1R. Intraportal moxonidine reduced plasma triglycerides by 23+/-3% within 10 min. Moxonidine inhibited hepatic triglyceride secretion by 75% compared to vehicle treatment. Tracer studies with 2H2O suggested that moxonidine inhibits de novo fatty acid synthesis. Thus, activation of I1R lowers plasma lipids, with the main site of action probably within the liver to reduce synthesis and secretion of triglycerides. More selective I1R agonists might provide monotherapy for hyperlipidemic hypertension.
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PMID:Lipid-lowering actions of imidazoline antihypertensive agents in metabolic syndrome X. 1641 66

Patients treated for hypertension are still at significantly elevated risk for cardiovascular complications when compared with normotensive patients, even when on antihypertensive therapy. In all fairness though, a majority of these patients have uncontrolled blood pressure. Blocking the renin-angiotensin-aldosterone system (RAAS) prevents or reverses cardiac remodelling and improves prognosis in cardiovascular disease beyond the effects on blood pressure (BP). Valsartan acts by selectively blocking the AT1-receptor and shows similar efficacy and improved tolerability compared with ACE inhibitors. This drug may provide additional benefits in controlling the cardiovascular complications of hypertension. Results of large clinical trials with valsartan, such as VALUE, Val-HEFT, VALIANT and ABCD-2V, are eagerly awaited.
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PMID:Valsartan and the renin-angiotensin-aldosterone system: blood pressure control and beyond. 1719 13


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