Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

High-salt (HS) diet is often associated with increased vascular resistance and arterial pressure; however, the effects of HS intake on the vascular control mechanisms of arterial pressure during pregnancy are unclear. We investigated whether a HS diet during pregnancy is associated with increases in vascular reactivity. Active stress was measured in aortic strips of virgin and normal pregnant Sprague-Dawley rats and a hypertensive pregnant rat model produced by reduction in uterine perfusion pressure (RUPP), fed either normal-sodium (NS, 1%) or HS diet (8%) for 7 days. In endothelium-intact strips, phenylephrine (Phe) caused a concentration-dependent contraction that was greater in RUPP rats than in normal pregnant or virgin rats and was significantly enhanced in pregnant/HS and RUPP/HS rats compared with pregnant/NS and RUPP/NS rats, respectively. Removal of the endothelium enhanced the Phe-induced stress slightly in virgin rats and significantly in pregnant/NS but not in pregnant/HS, RUPP/NS, or RUPP/HS. In endothelium-intact strips, acetylcholine (ACh) caused a concentration-dependent relaxation that was reduced in RUPP/NS (max, 31%) compared with pregnant/NS rats (max, 75%). ACh relaxation was further reduced in pregnant/HS rats compared with pregnant/NS rats and in RUPP/HS rats compared with RUPP/NS rats. Pretreatment of endothelium-intact strips with N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/L), to inhibit NO synthase, or with 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 10(-6) mol/L), to inhibit cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced contraction in pregnant/NS rats but not in pregnant/HS, RUPP/NS, or RUPP/HS rats. Basal and ACh-induced nitrite/nitrate production from aortic strips showed significant reduction in pregnant/HS rats compared with pregnant/NS rats but not in RUPP/HS rats compared with RUPP/NS rats. Sodium nitroprusside, an exogenous NO donor, caused relaxation of Phe contraction that was similar in virgin or pregnant rats on an NS or HS diet but was significantly reduced in RUPP/HS rats (ED(50) 6x10(-8) mol/L) compared with RUPP/NS rats (ED(50) 6x10(-9) mol/L). Thus, a HS diet in normal pregnant and RUPP rats is associated with increases in vascular reactivity. The enhanced vascular reactivity with the HS diet is possibly related to abnormalities in NO synthesis/release from the endothelium in normal pregnant rats and an additional decrease in the sensitivity of the smooth muscle to relaxation by NO in pregnant rats with reduced uterine perfusion pressure.
Hypertension 2001 Sep
PMID:High-salt diet enhances vascular reactivity in pregnant rats with normal and reduced uterine perfusion pressure. 1156 66

We tested the hypothesis that long-term application of a Ca2+ channel blocker would ameliorate the functional and morphological deterioration of the cerebral arteries during hypertension. Male spontaneously hypertensive rats (SHR) were fed a standard rat chow, containing a low (3 mg/kg/day) or high dose (6 mg/kg/day) of benidipine, a Ca2+ channel blocker, for 2 months. Using a cranial window, we examined responses of the basilar artery to acetylcholine, sodium nitroprusside, (-)-(3S,4R)-4-(N-acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ol (Y-26763; an opener of ATP-sensitive K+ channels), and (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632; an inhibitor of Rho-associated kinase). Mean arterial pressure of the control group was 193+/-5 mm Hg (mean+/-S.E.M.), while that of the low-dose benidipine group was 183+/-5 mm Hg and that of the high-dose group was 159+/-4 mm Hg. Dilator responses of the basilar artery to acetylcholine and Y-26763 were impaired in SHR compared with those of normotensive Wistar-Kyoto (WKY) rats and treatment with benidipine enhanced the vasodilator responses to acetylcholine and Y-26763 in SHR. Y-27632-induced dilatation of the basilar artery was enhanced in SHR compared to that in WKY rats and the vasodilatation was reduced by benidipine in SHR. Sodium nitroprusside caused similar dilatation of the basilar artery, in both WKY rats and the SHR control group, and benidipine did not affect nitroprusside-induced dilatation of the artery in SHR. The wall of the basilar artery was significantly thicker in SHR than in WKY rats and benidipine treatment reduced the wall thickness of the artery in SHR. These findings suggest that chronic treatment with a Ca2+ channel blocker may enhance the dilator capacity and reduce contractility of the basilar artery during hypertension. Benidipine may also ameliorate the morphological changes of the basilar artery in hypertension.
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PMID:Long-term effects of benidipine on cerebral vasoreactivity in hypertensive rats. 1190 6

Dietary potassium is known to cause reduction in blood pressure in several models of hypertension in human and animal studies but its haematological effects are not known. Here, experiments are designed to study the haematological effects of potassium adaptation (achieved by administering 0.75% KCl solution in drinking water for five weeks) in Wistar rats. The animals are divided into four groups comprising controls, potassium-adapted, renal hypertensive, and renal hypertensive with later adaptation to potassium. Packed cell volume (PCV) and platelet count (PC), whole blood and plasma viscosities, and platelet aggregation in the presence of sodium nitroprusside, levcromakalim, and glibenclamide, are studied. Results showed comparable PCV and PC in all groups. While relative whole blood viscosity was significantly higher (P<0.05) in the hypertensive group, relative plasma viscosity was similar in all groups. Adaptation significantly reduced (P<0.05) the tendency of platelets to aggregate to collagen. Sodium nitroprusside significantly reduced (P<0.05) the pro-aggregatory effects of collagen only in the control group. Neither of the potassium-channel modulators (levcromakalim, glibenclamide) caused any significant alteration in platelet response to collagen at the concentrations studied. Although these results suggest that potassium adaptation may not affect haemorheology, the reduced ability of platelets to aggregate--by mechanisms not clearly understood--has implications for reduced thromboembolism and the attendant cardiovascular sequelae.
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PMID:Haematological influences of potassium adaptation in normotensive and renally-hypertensive Wistar rats. 1211 8

Signals of individual muscle vasoconstrictor efferents of gastrocnemius muscle were recorded in narcotized cat during rise and fall of systemic arterial pressure induced by phenylephrine and sodium nitroprusside, respectively. In control, mean discharge rate of these efferents was 2.0 0.4 Hz. Phenylephrine (45 microg/kg) increased arterial pressure from 120.3 4.2 to 170.7 8.2 mm Hg. This increase was accompanied by a short-term (5-10 sec) decrease in discharge rate of muscle vasoconstrictor efferents to 0.5 0.3 Hz followed by virtually complete recovery of muscle discharge rate against the background of increased arterial pressure. Sodium nitroprusside (30 microg/kg) decreased arterial pressure from 132.8 6.2 to 64.1 4.3 mm Hg. Under these conditions the discharge rate of vasoconstrictor efferents increased to 3.5 0.6 Hz and remained at this level throughout the hypotension period (2-3 min). Unloading of baroreceptors (occlusion of the carotid artery) increased the discharge rate of muscle vasoconstrictor efferents throughout the occlusion period (up to 30 sec). Thus, blood pressure rise and drop induced asymmetric by their duration changes in the discharge responses of muscle vasoconstrictor efferents. Phenylephrine increased asymmetry of the vasoconstrictor component of the baroreflex and induced cumulative rise of discharge rate of muscle vasoconstrictor efferents in response to a series of short-term reversible blood pressure jumps caused by repeated occlusions of the abdominal aorta. Our findings extend our knowledge on the efferent component of the baroreflex regulation and on possible mechanisms of hypertension.
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PMID:Discharge activity of single muscle vasoconstrictor efferents in cats during opposite changes in arterial pressure. 1293 62

Endothelial cells can convert l-citrulline to l-arginine, the precursor of nitric oxide. The present study tests the hypothesis that a C-to-A nucleotide transversion (T1405N) in the gene-encoding carbamoyl-phosphate synthetase 1, the enzyme catalyzing the rate-limiting step in l-citrulline formation, influences nitric oxide metabolite concentrations or nitric oxide-mediated vasodilation in humans. Bradykinin (100, 200, and 400 ng/min) was infused via brachial artery in 106 (CC:AC:AA=40:54:12) healthy subjects. Sodium nitroprusside (1.6, 3.2, and 6.4 microg/min) was also infused in 87 (CC:AC:AA=31:46:10) subjects. Forearm blood flow was measured by plethysmography and blood samples were collected for tissue-type plasminogen activator antigen, nitric oxide metabolites, and cyclic GMP. There was a significant relationship between carbamoyl-phosphate synthetase 1 genotype and nitric oxide metabolites, such that nitric oxide metabolite concentrations were highest in individuals homozygous for the C allele (mean+/-SD, 14.0+/-8.5 micromol/L), lowest in individuals homozygous for the A allele (9.1+/-3.1 micromol/L), and intermediate (11.8+/-6.6 micromol/L) in heterozygotes (P=0.036). There was a significant effect of carbamoyl-phosphate synthetase 1 genotype on forearm blood flow during bradykinin (P=0.028), such that the vasodilator response was greatest in C allele homozygotes (22.2+/-9.1 mL/min/100 mL at 400 ng/min), least in A allele homozygotes (13.6+/-6.2 mL/min/100 mL), and intermediate (19.4+/-10.7 mL/min/100 mL) in heterozygotes. Similarly, carbamoyl-phosphate synthetase 1 genotype influenced forearm blood flow during nitroprusside (maximal flow 19.2+/-8.3, 18.1+/-8.3, and 11.5+/-4.9 mL/min/100 mL in the CC:AC:AA groups, respectively; P=0.022). In contrast, there was no effect of carbamoyl-phosphate synthetase 1 genotype on the nitric oxide-independent tissue-type plasminogen activator response to bradykinin (P=0.943). These data indicate that a polymorphism in the gene encoding carbamoyl-phosphate synthetase 1 influences nitric oxide production as well as vascular smooth muscle reactivity.
Hypertension 2004 Feb
PMID:Relationship between carbamoyl-phosphate synthetase genotype and systemic vascular function. 1471 56

Some cardiovascular risk factors, such as hypertension and insulin resistance, are associated with endothelial dysfunction. Insulin regulates both in vitro and in vivo expression of endothelial nitric oxide synthase (eNOS) via a pathway involving insulin receptor substrate-1 (IRS-1) and phosphatidylinositol-3 kinase. Recently, we found that human endothelial cells obtained from carriers of the Arg(972) IRS-1 polymorphism exhibited reduced eNOS expression in response to chronic exposure to insulin. A reduction in eNOS expression would be expected to be associated with impaired endothelium-dependent vasodilation. To investigate a possible relationship between Arg(972) IRS-1 polymorphism and endothelial dysfunction in vivo, we enrolled a cohort of 100 never-treated hypertensive subjects. Endothelium-dependent and endothelium-independent vasodilation were assessed by increasing doses of acetylcholine and sodium nitroprusside. IRS-1 polymorphism was detected by PCR. The allelic frequency of the Arg(972) IRS-1 variant was 8.0%. Stratifying subjects according to IRS-1 genotype, we observed that acetylcholine-stimulated forearm blood flow was significantly (P < 0.0001) lower in Gly/Arg heterozygous carriers than in Gly/Gly carriers (11.3 +/- 4.4 vs. 14.7 +/- 5.9 ml/100 ml(-1) of tissue per min(-1)). Sodium nitroprusside caused comparable increments in forearm blood flow in both groups (12.9 +/- 2.4 vs. 13.3 +/- 3.5 ml/100 ml(-1) of tissue per min(-1)). Our data strongly suggest that, by inducing endothelial dysfunction, the Arg(972) IRS-1 polymorphism may contribute to the genetic predisposition to develop cardiovascular disease.
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PMID:Impaired endothelial function in never-treated hypertensive subjects carrying the Arg972 polymorphism in the insulin receptor substrate-1 gene. 1524 Jun 53

Endothelial dysfunction has been demonstrated to occur in small arteries from patients with type 2 diabetes and hypertension. The effects of angiotensin II receptor blockade on vessel function were examined using pressure myography in a randomized 12-week double-blind placebo-controlled parallel group study using candesartan cilexitil. The maximal vascular response to acetylcholine (Ach) was impaired at baseline and improved with candesartan. This improvement was primarily caused by an effect in the nitric oxide component of Ach-mediated dilatation. The degree of endothelial dysfunction directly correlated with serum low-density lipoprotein cholesterol levels. Sodium nitroprusside-induced endothelium-independent dilatation was reduced in diabetic patients and intervention with candesartan lead to an improvement in EC50 with no change in maximal response. Vasoconstriction to norepinephrine was normal and did not change with intervention, but responses to angiotensin II were reduced after candesartan in diabetic patients. These results demonstrate that even brief treatment with angiotensin II receptor blockade is associated with a significant improvement in resistance vessel endothelial function.
Hypertension 2005 Feb
PMID:Effects of angiotensin type-1 receptor antagonism on small artery function in patients with type 2 diabetes mellitus. 1563 48

We compared the perioperative profiles of patients undergoing unilateral phaeochromocytoma resection performed by open adrenalectomy with those performed by laparoscopic adrenalectomy. Data was collected prospectively on 24 patients (12 open, 12 laparoscopic). All patients underwent extensive preoperative medical preparation with phenoxybenzamine and beta-blockers. The final preoperative dose of phenoxybenzamine was similar in each group (laparoscopic 119+/-60 mg/day, open 100+/-25 mg/day). Intraoperative haemodynamic instability was assessed by the requirement for therapeutic intervention. More haemodynamic instability was observed in the laparoscopic group but the differences were not statistically significant. Sodium nitroprusside use to treat hypertension (systolic blood pressure >180 mmHg) was more frequent and the duration of the infusions longer in the laparoscopic group; high dose beta-blocker therapy with atenolol and/or esmolol to treat intraoperative tachycardia (heart rate >90) was also more frequent in the laparoscopic group. The small sample size of the study limited the ability to detect a true difference. Blood loss was greater in the open adrenalectomy group but the difference was not significant. The operating time was significantly longer (236+/-78 vs 147+/-47 min, P<0.01) but the duration of postoperative hospitalization was significantly shorter (5+/-2 vs 11+/-4 days, P<0.01) in the laparoscopic group. Postoperative complications were not significantly different. There were no perioperative deaths. Overall, we observed more haemodynamic instability in patients undergoing laparoscopic resection but were unable to demonstrate a statistically significant difference. In our experience, laparoscopic adrenalectomy has the advantage of a shorter time to discharge from hospital.
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PMID:A comparison of open and laparoscopic approaches to adrenalectomy in patients with phaeochromocytoma. 1595 20

Excessive hypertension can challenge the brain's capacity to autoregulate cerebral blood flow, and can aggravate increased intracranial pressure (ICP) and cerebral edema. Hypotension may worsen ischemic damage in marginally perfused tissue, and in some cases can trigger cerebral vasodilation and ICP plateau waves. There is a lack of high-quality data regarding optimal BP management in these conditions. Existing guidelines for target BP levels are based largely on class III evidence. Class I data only exist for enteral candesartan and nimodipine use in acute ischemic stroke and aneurismal subarachnoid hemorrhage (SAH), respectively, and for parenteral magnesium use in eclampsia. Class II data exist for reducing BP to <180/105 mmHg in patients with ischemic stroke who are treated with intravenous tissue plasminogen activator, for elevating systolic BP to 180-220 mmHg in SAH patients with symptomatic vasospasm, and for maintaining cerebral perfusion pressure (CPP)>60 mmHg in traumatic brain injury. Short-acting continuous-infusion agents with a reliable dose-response relationship and favorable safety profile are desirable. To reduce BP, labetalol, esmolol, and nicardipine best meet these criteria. Sodium nitroprusside should be avoided in most neurological emergencies because of its tendency to raise ICP and cause toxicity with prolonged infusion. To elevate BP, the preferred agents are phenylephrine, dopamine, and norepinephrine.
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PMID:Optimizing blood pressure in neurological emergencies. 2751 96

Endothelial dysfunction is important in the pathophysiology of preeclampsia. No study has examined endothelial function sequentially at different gestations before development of the clinical syndrome and after delivery (to compare maternal from placental influences). We sought to determine whether endothelial function changes before the clinical development of preeclampsia. We measured skin microvascular function using iontophoresis of acetylcholine and sodium nitroprusside, and laser Doppler imaging at 22, 26, 34 weeks' gestation and 6 weeks postpartum in women identified as being at increased risk of preeclampsia, based on uterine artery Doppler waveforms at 18 to 20 weeks, and controls with normal Doppler waveforms. Fifty-four women remained normotensive and preeclampsia developed in 15. In normotensive and preeclamptic women, acetylcholine responses were augmented during pregnancy compared with postpartum responses (P<0.001). Sodium nitroprusside responses were augmented during pregnancy compared with those postpartum (P<0.005) in preeclamptic women only. Microvascular responses were augmented in women in whom preeclampsia developed, compared with those in normotensive women, at 26 and 34 weeks for acetylcholine (P<0.05 and P<0.001, respectively) and at 22 and 26 weeks for sodium nitroprusside (P<0.05 and P<0.02, respectively). Postpartum acetylcholine and sodium nitroprusside responses were not significantly different between preeclamptic and normal women. Microvascular responses are enhanced during pregnancy in women in whom preeclampsia develops to a level above that seen in normotensive women. These changes precede the onset of clinical disease and might be related to a compensatory increased sensitivity of the microcirculation to nitric oxide.
Hypertension 2005 Nov
PMID:Changes in endothelial function precede the clinical disease in women in whom preeclampsia develops. 1649 Aug 38


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