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

Acute experimental reduction of renal blood flow decreases the renal blood oxygenation level-dependent (BOLD) MRI signal in animals. Angiotensin II also reduces renal blood flow, but the ability of BOLD MRI to dynamically detect this response has not yet been investigated in humans. Six healthy male volunteers underwent an individual dose-finding study to identify the intravenous doses of angiotensin II, norepinephrine, and sodium nitroprusside necessary to induce a 15-mm Hg peak mean arterial blood pressure change. MRI studies followed within 3 weeks, when angiotensin II (8.8+/-1.4 ng/kg), norepinephrine (52+/-12 ng/kg), and sodium nitroprusside (2.0+/-0.3 microg/kg) were given twice in an unblocked, randomized sequence while imaging experiments were performed on a 1.5-T Siemens Sonata. A multiecho echo-planar imaging sequence was used to acquire T2* maps with a temporal resolution of 1 respiratory cycle. Averaged over a renal cortex dominated region of interest, angiotensin II caused a shortening of T2* between 6% and 10%. Sodium nitroprusside and norepinephrine, although of equal potency concerning blood pressure responses, did not alter the renal BOLD signal. The renal BOLD response to angiotensin II appeared with short onset latency (as early as 10 seconds after peripheral intravenous angiotensin II bolus administration) suggesting that this response is a consequence of altered perfusion rather than increased renal oxygen consumption. The methods described here are suitable to assess renal responsiveness to angiotensin II and may, thus, be of great value in human hypertension research.
Hypertension 2006 Jun
PMID:Angiotensin II decreases the renal MRI blood oxygenation level-dependent signal. 1661 41

Treatment of erectile dysfunction (ED) in hypertensive subjects remains to be formally established. There is currently no standardized treatment for ED in hypertensive subjects. In this study, we tested our hypothesis that hypotensive drugs would improve impaired relaxation in the corpus cavernosum of spontaneously hypertensive rats (SHR). Ten-week-old SHR was treated with amlodipine, imidapril or hydralazine for 4 weeks. Although all three drugs achieved an equivalent decrease in systolic blood pressure (SBP), only amlodipine and imidapril induced an increase in relaxation in response to electrical field stimulation (EFS) of the corpus cavernosum. In the case of amlodipine, this effect was dose- and SBP-dependent. Nitric oxide (NO)-dependent relaxation was increased by amlodipine over a wide range of EFS frequencies, was increased by imidapril at low EFS frequencies, and was decreased by hydralazine. Carbon monoxide (CO)-dependent relaxation was only increased by hydralazine, and this increase occurred over a wide range of frequencies. The NOx and cGMP levels in the EFS-stimulated corpus cavernosum were increased by amlodipine. Amlodipine did not affect the thiobarbituric acid-reacting substance levels in the serum and the corpus cavernosum, but did decrease superoxide dismutase activity in the tissue. Imidapril and hydralazine inhibited the acetylcholine-induced relaxation in the corpus cavernosum. Sodium nitroprusside-induced relaxation in the tissue was increased by amlodipine. All three agents similarly inhibited the phenylephrine-induced contraction. These results suggest that impaired neurogenic relaxation in the corpus cavernosum of SHR is improved by amlodipine and imidapril through an increase in the synthesis and/or release of neuronal NO, but not CO, and presumably the inhibited detumescence of erection, which is induced by norepinephrine being released from sympathetic neuron. These findings indicate that amlodipine and imidapril may ameliorate the decreased relaxation of cavernous smooth muscle in the setting of hypertension.
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PMID:Treatment with hypotensive agents affects the impaired relaxation of the penile corpus cavernosum in hypertensive rats. 1704 65

Nitric oxide (NO) is an important bioactive molecule derived from endogenous or exogenous sources. NO can exhibit genotoxicity through the formation of reactive nitrogen species. Nitric oxide releasing compounds, such as sodium nitroprusside, are widely used for the therapy of hypertension and other disorders. Here we have characterized the mutagenicity of sodium nitroprusside in mouse embryo fibroblasts carrying the cII mutation reporter gene. Sodium nitroprusside dose-dependently increased the cII mutant frequency to levels approximately 5-fold above background. The mutational spectrum induced by sodium nitroprusside was characterized by an increase in the fraction of G-->T transversion mutations (P < 0.003) but the proportion of transition mutations was not increased. We discuss the potential origin of the G-->T mutations induced by this compound in mammalian cells.
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PMID:Mutagenesis induced by the nitric oxide donor sodium nitroprusside in mouse cells. 1715 87

This study investigated relaxation of vascular smooth muscle by acetylcholine, bradykinin and protease-activated receptor 2 (PAR-2) to characterise endothelial dysfunction in spontaneously hypertensive mice (BPH/2). We hypothesised that PAR-2 induced vasodilation would be preserved in BPH/2 despite the presence of hypertension and impaired vasodilator responses to acetylcholine and bradykinin. Mean arterial blood pressure (MAP), heart rate and locomotor activity were assessed in conscious mice over 24-h periods by radiotelemetry. Relaxation responses of small mesenteric arteries to acetylcholine, bradykinin and the PAR-2 agonist, 2-furoyl-LIGRLO-amide (2fly), were assessed using wire myographs. MAP and heart rate of BPH/2 were 15 and 18%, respectively, higher than in controls (BPN/3). BPH/2 also exhibited increased locomotor activity. Maximal relaxations of arteries by acetylcholine and bradykinin in BPH/2 were reduced by 25-50% relative to BPN/3. In contrast, relaxation responses to 2fly were only slightly (6%), albeit significantly, reduced. Sodium nitroprusside-induced relaxations were not different between strains. Treatment of BPH/2 arteries with inhibitors of calcium-activated K(+) channels was sufficient to block persistent 2fly- and residual ACh- and bradykinin-induced relaxations, whereas NO synthase inhibitor failed to inhibit these relaxations. In BPH/2 mice, vascular smooth muscle relaxation by PAR-2 is well preserved despite the presence of hypertension and impaired vasodilation responses to acetylcholine and bradykinin.
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PMID:Persistence of PAR-2 vasodilation despite endothelial dysfunction in BPH/2 hypertensive mice. 1731 44

The purpose of this study was to evaluate endothelial function in patients with periodontitis. We evaluated forearm blood flow responses to acetylcholine and sodium nitroprusside in patients with periodontitis who had no other cardiovascular risk factors (32 men; 25+/-3 years of age), in a normal control group (20 men; 26+/-3 years of age), and in hypertensive patients with periodontitis (28 men and 10 women; 56+/-12 years of age) and without periodontitis (control group; 18 men and 6 women; 54+/-13 years of age). Forearm blood flow was measured using strain-gauge plethysmography. Circulating levels of C-reactive protein and interleukin-6 were significantly higher in the periodontitis group than in the control group. Both in healthy and hypertensive subjects, forearm blood flow responses to acetylcholine were significantly smaller in the periodontitis group than in the control group. Sodium nitroprusside-stimulated vasodilation was similar in the 2 groups. Periodontal therapy reduced serum concentrations of C-reactive protein and interleukin-6 and augmented acetylcholine-induced vasodilation in periodontitis patients with and without hypertension. After administration of N(G)-monomethyl-L-arginine, an NO synthase inhibitor, forearm blood flow response to acetylcholine was similar before and after treatment. These findings suggest that periodontitis is associated with endothelial dysfunction in subjects without cardiovascular risk factors, as well as hypertensive patients, through a decrease in NO bioavailability and that systemic inflammation may be, at least in part, a cause of endothelial dysfunction, leading to cardiovascular diseases.
Hypertension 2008 Feb
PMID:Periodontal infection is associated with endothelial dysfunction in healthy subjects and hypertensive patients. 1803 79

Approximately 72 million people in the US experience hypertension. Worldwide, hypertension may affect as many as 1 billion people and be responsible for approximately 7.1 million deaths per year. It is estimated that approximately 1% of patients with hypertension will, at some point, develop a hypertensive crisis. Hypertensive crises are further defined as either hypertensive emergencies or urgencies, depending on the degree of blood pressure elevation and presence of end-organ damage. Immediate reduction in blood pressure is required only in patients with acute end-organ damage (i.e. hypertensive emergency) and requires treatment with a titratable, short-acting, intravenous antihypertensive agent, while severe hypertension without acute end-organ damage (i.e. hypertensive urgency) is usually treated with oral antihypertensive agents. The primary goal of intervention in a hypertensive crisis is to safely reduce blood pressure. The appropriate therapeutic approach of each patient will depend on their clinical presentation. Patients with hypertensive emergencies are best treated in an intensive care unit with titratable, intravenous, hypotensive agents. Rapid-acting intravenous antihypertensive agents are available, including labetalol, esmolol, fenoldopam, nicardipine and sodium nitroprusside. Newer agents, such as clevidipine and fenoldopam, may hold considerable advantages to other available agents in the management of hypertensive crises. Sodium nitroprusside is an extremely toxic drug and its use in the treatment of hypertensive emergencies should be avoided. Similarly, nifedipine, nitroglycerin and hydralazine should not to be considered first-line therapies in the management of hypertensive crises because these agents are associated with significant toxicities and/or adverse effects.
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PMID:Treatment of acute severe hypertension: current and newer agents. 1825 7

Sodium nitroprusside (SNP) is a water-soluble iron nitrosyl complex clinically used as a powerful vasodilator for treatment of hypertension; and, in basic research, it has been used to mainly investigate the cytotoxic effects of nitrosative stress. Although NO is considered a pharmacologically active molecule, not all of the biological effects of SNP are dependent on its NO moiety. To elucidate the molecular executioner(s) responsible for SNP cytotoxicity, this study determines the involvement of oxidative stress in p53 activation and apoptotic induction elicited by SNP in SH-SY5Y neuroblastoma cells. We demonstrate that proapoptotic activity of SNP is independent of NO production, because SNP and its 2-day light-exhausted compound SNP(ex) trigger apoptosis to the same extent. We provide evidence for the occurrence of oxidative stress and oxidative damage during both SNP and SNP(ex) exposure and demonstrate that iron-derived reactive oxygen species (ROS) are the genuine mediators of their cytotoxicity. We show that p53 is equally activated upon both SNP and SNP(ex) treatments. Moreover, as demonstrated by small interfering RNA experiments, we indicate its primary role in the induction of apoptosis, suggesting the ineffectiveness of NO in its engagement. The attenuation of p53 levels, obtained by oxy-radical scavengers, is consistent with the recovery of cell viability and ROS decrease, demonstrate that SNP-mediated p53 activation is an event triggered by ROS and/or ROS-mediated damages. Together, our results suggest that investigations of the physiopathological effects of SNP should consider the role of ROS, other than NO, particularly in some conditions such as apoptotic induction and p53 activation.
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PMID:Reactive oxygen species mediate p53 activation and apoptosis induced by sodium nitroprusside in SH-SY5Y cells. 1867 76

The arterial baroreflex is a fundamental reflex that buffers rapid changes in arterial blood pressure (BP) via regulation of the heart rate and sympathetic nerve activity to the vasculature. In adults a sigmoidal relationship between BP and both heart rate and sympathetic nerve activity is well documented. Its role in blood pressure control before birth is unclear. Preterm babies have a high incidence of low BP, especially in the first few days of life, which could be related, in part, to immaturity of the baroreflex. In the present study, we investigated the baroreflex control of fetal heart rate and renal sympathetic nerve activity (RSNA) in preterm fetal sheep in utero (102 +/- 1 days of gestation; term 140 days). Phenylephrine was associated with a significant increase in BP from 38 +/- 2 to 58 +/- 3 mmHg and a decrease in heart rate (HR) from 177 +/- 4 to 116 +/- 8 beats per minute (bpm). Sodium nitroprusside was associated with a significant fall in BP from 38 +/- 2 to 26 +/- 1 mmHg and an increase in HR from 182 +/- 4 to 274 +/- 8 bpm. However, the time between the 50% changes in BP and HR was significantly greater after hypotension than hypertension (31 +/- 8 s vs. 14 +/- 5 s, P < 0.05). No significant changes in RSNA occurred with either stimulus. This suggests that there are different maturational tempos for the components of the central autonomic response to altered blood pressure.
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PMID:Is baroreflex control of sympathetic activity and heart rate active in the preterm fetal sheep? 1910 68

Hypertension (HTN) is one of the most common chronic medical conditions, affecting nearly 72 million people in the United States. A systolic blood pressure (BP) > 180 mm Hg or a diastolic BP > 120 mm Hg is considered a "hypertensive crisis." Hypertensive crises are categorized as either hypertensive emergencies or urgencies depending on the degree of BP elevation and presence of end-organ damage. The primary goal of intervention in a hypertensive crisis is to safely reduce BP. Immediate reduction in BP is required only in patients with acute end-organ damage (ie, hypertensive emergency). This requires treatment with a titratable shortacting intravenous (IV) antihypertensive agent, while severe HTN with no acute end-organ damage (ie, hypertensive urgency) is usually treated with oral antihypertensive agents. Patients with hypertensive emergencies are best treated in an intensive care unit (ICU) with titratable IV hypotensive agents. Rapid-acting IV antihypertensive agents are available, including clevidipine, labetalol, esmolol, fenoldopam, nicardipine, and sodium nitroprusside. Newer agents such as clevidipine have considerable advantages compared with other available agents in the management of hypertensive crises. Sodium nitroprusside is an extremely toxic drug, and its use in the treatment of hypertensive emergencies should be avoided. Likewise, nifedipine, nitroglycerin, and hydralazine should not to be considered first-line therapies in the management of hypertensive crises because these agents are associated with significant toxicities and/or side effects.
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PMID:The diagnosis and treatment of hypertensive crises. 1917 9

Both hypotension and hypertension aggravate the damage of reperfusion injury after reconstructive microsurgery. The purpose of this study is to establish a theoretical guide for postoperative blood pressure control in optimizing the cutaneous perfusion and flap survival. Systemic arterial pressure was altered by the intravenous infusion of saline, sodium nitroprusside, phentolamine, and phenylephrine in thirty-two 280-350 g anesthetized Sprague Dawley rats. Power spectral analysis of systemic arterial pressure (SAP) and laser Doppler flowmetry (flux) of epigastric skin were used to reveal the blood pressure and cutaneous blood flow variabilities. Nonparallel responses of cutaneous perfusion and blood pressure were found. The baseline SAP and flux were 126.0 +/- 1.4 mmHg and 57.2 +/- 1.8 au, respectively. Sodium nitroprusside and phentolamine significantly decreased the SAP (71.1 +/- 2.7 and 70.5 +/- 1.5 mmHg, P < 0.0001). However, the corresponding responses in cutaneous perfusion were opposite (56.2 +/- 3.1 au, P = 0.7389 and 36.2 +/- 2.3 au, P < 0.0001). Phenylephrine significantly increased the SAP (171.7 +/- 3.0 mmHg, P < 0.0001) but the flux of epigastric skin was decreased (44.4 +/- 2.6 au, P < 0.0001). Phentolamine and phenylephrine showed negative effects on the systemic cardiac and vascular sympathetic modulations. Sodium nitroprusside had a trend in increasing systemic vasomotor activity. We suggested not using vasoconstrictors in treating intra and postoperative hypotension associated with free flap transfer. Nitric oxide donors are superior to alpha-adrenoceptor antagonists in preserving the cutaneous flap perfusion when treating postoperative hypertension.
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PMID:Nonparallel cutaneous microcirculatory responses to pharmacologic alterations of systemic arterial pressure in rats. 1929


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