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)

Despite the availability of diagnostic modalities such as transesophageal echocardiography, computed tomography or magnetic resonance imaging up to 30% of patients with acute aortic dissection remain undiagnosed before death. A novel immunoassay of serum smooth muscle myosin heavy chain was recently developed as a potential diagnostic tool for the detection of aortic dissection. The immunoassay was applied in two patients with an acute chest pain syndrome but no initial clinical suspicion of aortic disease. In both patients myocardial ischemia was ruled out by laboratory, electrocardiographic and echocardiographic examinations. In the first patient both dilation of the aorta and long-standing arterial hypertension were known; however, it was not before 48 h until dissection was suspected and a spiral-CT was performed demonstrating a localized ascending aortic dissection. At this time (48 h after onset of symptoms) the smooth muscle myosin heavy chain concentration in the serum was close to normal. In the other patient there was neither a suggestive history nor any clinical sign of aortic dissection. Widening of the abdominal aortic wall on an ultrasound examination was the key to the incidental diagnosis of a clinically unsuspected type B dissection. The serum test 12 h after onset of pain revealed elevated (diagnostic) serum levels of smooth muscle myosin heavy chains. Both cases exemplify important gaps in the diagnostic strategy for the detection of acute aortic dissection. A novel immunoassay for smooth muscle myosin heavy chains provides rapid and reliable diagnostic information especially in patients without clinically suspected aortic dissection and may avoid limitations in the diagnostic work-up of patients with acute aortic disease, if used early in the evaluation of patients with chest pain syndromes.
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PMID:[Increased serum concentration of myosin heavy chain in aortic dissection: discussion of 2 cases]. 932 78

Changes in unloaded maximum shortening velocity (Vmax) and myosin isoenzymes (MI) composition of rat left ventricular muscle were examined in the 8-week or 16-week Goldblatt hypertensive (H8, H16) and hypertension-regressive rats (R8). The Vmax was estimated by extrapolation to zero afterload from the tension-velocity curve of left ventricular papillary muscle, while the MI composition (V1, V2 and V3) was separated by polyacrylamide gel electrophoresis and determined by densitometry. The results showed that: (1) A slow age-dependent shift to V3 and a decrease in Vmax were observed in 16- and 24-week-old rats (S8, S16), in which V1/V3 ratio was decreased respectively by 38.9% and 61.0% and Vmax was decreased respectively by 8.3% and 13.3% when compared with that of the 8-week-old rats (S0). (2) There was a significant decrease in V1/V3 ratio and Vmax in 8-week (H8) and 16-week (H16) hypertension induced hypertrophic left ventricular muscle as evidenced by the fact that the V1/V3 ratio decreased by 84.4% and 93.5% and Vmax decreased by 33.3% and 48.3% in H8 and H16 as compared with that of the control rats (S0). (3) There was a partial recovery in Vmax and V1/V3 ratio in (R8) group rats. (4) The Vmax was positively correlated with the level of V1 (r = 0.9215, P < 0.01) and negatively with the level of V3 (r = 0.9071, P < 0.01) as analyzed in all the six experimental groups of a total of 48 rats (S0, S8, S16, H8, H16, R8). In conclusion, a significant shift of the myosin isoenzymes towards low ATPase activity V3 might be the biochemical mechanism responsible, at least in part, for the decrease in maximum shortening velocity in the hypertrophic left ventricular muscle induced by pressure overload.
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PMID:[Changes in myosin isoenzymes composition and the maximum shortening velocity in hypertrophic left ventricular muscle of rats]. 938 1

The principal stimulus that evokes pulmonary hypertension is chronic alveolar hypoxia. Pulmonary hypertension is associated with remodeling of the vessel walls, involving hypertrophy and hyperplasia of pulmonary arterial smooth muscle (PASM) and a concomitant increase in the deposition of connective tissue, resulting in increased wall thickness. The purpose of the present study was to determine the effect of hypoxia-induced hypertension on the structure and function of PASM. Experiments were designed to determine whether hypoxia-induced pulmonary hypertension is associated with alterations in PASM: 1) reactivity to a variety of agonists, 2) contractile protein proportions and isoforms, and 3) structural properties. Young adult male rats were made hypoxic by lowering the fraction of inspired O2 (10%) for 14 days. Pulmonary arterial segments were isolated and dose-response curves to various agonists (high K+, norepinephrine, serotonin, angiotensin II, and adenosine) were generated. Gel electrophoresis was used to measure changes in the relative amounts of actin or myosin and of myosin heavy chain (MHC) isoforms. Structural changes were correlated with the pharmacological and biochemical data. Hypoxia-induced pulmonary hypertension caused a general decreased reactivity, an increase in the proportion of nonmuscle to muscle MHC isoforms in PASM, and an increase in arterial wall thickness with PASM hypertrophy or hyperplasia.
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PMID:Myosin isoform shifts and decreased reactivity in hypoxia-induced hypertensive pulmonary arterial muscle. 961 93

Abnormal smooth muscle contraction may contribute to diseases such as asthma and hypertension. Alterations to myosin light chain kinase or phosphatase change the phosphorylation level of the 20-kDa myosin regulatory light chain (MRLC), increasing Ca2+ sensitivity and basal tone. One Rho family GTPase-dependent kinase, Rho-associated kinase (ROK or p160(ROCK)) can induce Ca2+-independent contraction of Triton-skinned smooth muscle by phosphorylating MRLC and/or myosin light chain phosphatase. We show that another Rho family GTPase-dependent kinase, p21-activated protein kinase (PAK), induces Triton-skinned smooth muscle contracts independently of calcium to 62 +/- 12% (n = 10) of the value observed in presence of calcium. Remarkably, PAK and ROK use different molecular mechanisms to achieve the Ca2+-independent contraction. Like ROK and myosin light chain kinase, PAK phosphorylates MRLC at serine 19 in vitro. However, PAK-induced contraction correlates with enhanced phosphorylation of caldesmon and desmin but not MRLC. The level of MRLC phosphorylation remains similar to that in relaxed muscle fibers (absence of GST-mPAK3 and calcium) even as the force induced by GST-mPAK3 increases from 26 to 70%. Thus, PAK uncouples force generation from MRLC phosphorylation. These data support a model of PAK-induced contraction in which myosin phosphorylation is at least complemented through regulation of thin filament proteins. Because ROK and PAK homologues are present in smooth muscle, they may work in parallel to regulate smooth muscle contraction.
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PMID:Different molecular mechanisms for Rho family GTPase-dependent, Ca2+-independent contraction of smooth muscle. 972 79

The importance of the loss of ovarian function to the progression of hypertension and heart disease in women is controversial. We investigated whether ovariectomy would accelerate development of hypertension, congestive heart failure, and neurohumoral activation in adult spontaneous hypertension heart failure (SHHF) rats, a genetic model of heart failure. Six months after ovariectomy, no significant differences between control and ovariectomized rats were seen in systolic or diastolic blood pressure, left ventricular fractional shortening by echocardiography, or heart weight. Percent V1 myosin isozyme was significantly lower in ovariectomized rats. Northern blot analysis failed to show significant differences between groups in expression of hepatic angiotensinogen, renal renin, or left ventricular atrial or brain natriuretic peptide mRNA. In a second experiment, serial measures of systolic pressure and left ventricular shortening fractions failed to document a significant difference between control and ovariectomized rats as they developed heart failure, although there was a significant decline in shortening fraction in both groups at the age when regular estrous cycling naturally ceases. Survival time was similar between groups. In summary, ovariectomy of adult SHHF rats does not appear to affect the progression of genetically programmed hypertension and heart failure in this model.
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PMID:Effect of ovariectomy in heart failure-prone SHHF/Mcc-facp rats. 984 86

Angiotensin-converting enzyme (ACE) inhibitors have proven an effective means to control hypertension and manage cardiac hypertrophy. It is presently unknown if newer specific angiotensin II subtype 1 receptor (AT1R) antagonists are as effective or more effective in treating these conditions compared with ACE inhibitors. There is evidence that these classes of drugs may affect cardiac hypertrophy by different mechanisms. This study compared the effect of irbesartan, an AT1R antagonist, with that of captopril, an ACE inhibitor, on expression of early genetic markers of cardiac hypertrophy in lean male SHHF/Mcc-fa(cp) rats. SHHF/Mcc-fa(cp) rats (n = 10/group) were given captopril (100 mg/kg/day), irbesartan (50 mg/kg/day), or placebo for 16 weeks. Irbesartan and captopril significantly reduced systolic pressure and produced similar rightward shifts in the angiotensin I dose-response curve. Renal renin gene expression was increased 8.6-fold by irbesartan and 17.7-fold by captopril. The only effect on echocardiographic findings was a similar decrease in aortic peak velocity, an index of systolic function, by both treatments. Early markers of cardiac hypertrophy were significantly attenuated by both drugs. Both drugs produced marked and equivalent reductions in left ventricular atrial natriuretic peptide (ANP) messenger RNA (mRNA) levels compared with controls. This decrease in ANP gene expression was accompanied by a decrease in plasma ANP concentration in the treatment groups. The shift from V1 to V3 myosin isozymes was similarly decreased in both treatment groups, compared with controls. These data suggest that captopril and irbesartan are similarly effective in controlling expression of genes associated with ventricular hypertrophy in heart failure-prone SHHF/Mcc-fa(cp) rat.
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PMID:Comparison of irbesartan with captopril effects on cardiac hypertrophy and gene expression in heart failure-prone male SHHF/Mcc-fa(cp) rats. 1006 82

Concern over dietary fat in processed meats led to the passage of the '40 per cent' rule in the United States. Substitution of NaCl, linked to hypertension, with divalent chloride salts such as MgCl2 and CaCl2 has shown limited success. Early studies showed that these divalent salts had a deleterious effect on the functional properties of meat when used at product levels that resulted in high aqueous phase ionic strengths (0.4-0.6). However, our research focus has been to determine the utility of low levels (0.05 per cent) of MgCl2, CaCl2 and ZnCl2 in improving the functional properties of processed meats. Effects of divalent salts have been evaluated in turkey breast and thigh minces, beef model systems, and frankfurter formulations containing heart muscle. To determine if time postmortem affects muscle's response to divalent cations, salts were added to broiler thigh muscle in the early postmortem period. The important findings were (1) MgCl2 increased myosin solubility, (2) CaCl2 enhanced gel forming ability in cooked batters, and (3) ZnCl2 dramatically decreased myosin solubility in the absence of food-grade phosphate (sodium tripolyphosphate).
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PMID:Improvement of muscle protein functionality in processed meats by magnesium and other divalent chloride salts. 1019 95

The aim of this study was to clarify the differences between the angiotensin II type 1 (AT1) receptor antagonist and the angiotensin-converting enzyme (ACE) inhibitor on smooth muscle and nonmuscle myosin heavy chain isoforms in aortic smooth muscle cells of Wistar-Kyoto rats and spontaneously hypertensive rats. All 4 myosin heavy chain isoforms are heterogeneously expressed in the smooth muscle cells of the aortic tunica media in 20-week-old rats, and the contractile-type myosin heavy chains are highly expressed in smooth muscle cells of the aortic tunica media compared with the synthetic-type myosin heavy chains. Both the AT1 receptor antagonist and the ACE inhibitor had the same effects on hemodynamics, smooth muscle cell hypertrophy and proliferation, fibrosis, and vascular remodeling in spontaneously hypertensive rats. However, the AT1 receptor antagonist had a more potent effect on the downregulation of the synthetic-type myosin heavy chains than the ACE inhibitor in spontaneously hypertensive rat aortic tunica media. In contrast, these effects of the AT1 receptor antagonist and the ACE inhibitor on hemodynamics, morphology, fibrosis, and expression of myosin heavy chain isoforms in smooth muscle cells of the aortic tunica media were not observed in Wistar-Kyoto rats. Thus, within 6 weeks, the AT1 receptor antagonist might modulate the cellular composition of myosin heavy chain isoforms in smooth muscle cells more efficiently than the ACE inhibitor, without morphological changes in the spontaneously hypertensive rat aorta.
Hypertension 1999 Apr
PMID:Angiotensin II type 1 receptor antagonist downregulates nonmuscle myosin heavy chains in spontaneously hypertensive rat aorta. 1020 33

The importance of endogenous and exogenous estrogen levels to the development of cardiovascular disease in women in controversial. The purpose of our study was to examine the effect of estrogen on the development of hypertension, cardiac hypertrophy, ventricular function, and gene expression for atrial natriuretic peptide (ANP) and components of the renin angiotensin system in spontaneously hypertensive heart failure rats (SHHF/Mcc- facp). Development of hypertension was prevented in 3-month-old ovariectomized rats receiving subcutaneous 17 beta -estradiol implants (EST) compared to ovariectomized (OVX) and controls (CON). EST had the least left ventricular hypertrophy, CON were intermediate, and OVX had the most (P<0.05), correlating well with systolic blood pressure. OVX had significantly lower percentage V(1)myosin isoform compared to EST and CON, indicating reversion to a more immature phenotype associated with hypertrophy. Similarly, OVX had decreased percentage left ventricular shortening fraction by echocardiography compared to EST and CON. These changes were not accompanied by alterations in plasma ANP, or in expression of mRNA for left ventricular ANP, renal renin, or hepatic angiotensinogen. Serum angiotensin converting enzyme activity was lower in EST compared to CON or OVX. When 17 beta -estradiol was given to 17-month-old rats that had naturally ceased estrous cycling, there was no effect on hypertension, progression of cardiac functional decline, or survival. In conclusion, estradiol treatment given prior to the development of hypertension in SHHF prevented left ventricular hypertrophy and hypertension. Development of congestive heart failure was not delayed if 17 beta -estradiol was begun in the post-menopausal period. Effectiveness of estrogen therapy may depend on age or whether hypertension is already established at the time treatment is begun.
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PMID:Effect of ovariectomy and estrogen replacement on cardiovascular disease in heart failure-prone SHHF/Mcc- fa cp rats. 1042 50

We addressed the hypothesis that hypercaloric diets induce hyperkinetic hypertension irrespective of day-night cycle and locomotor activity that is associated with altered cardiac myosin isozymes. Normotensive rats with implanted radiotelemetry pressure transducers were fed increasing amounts of coconut fat (8, 16, and 24%, each for 2 wk) corresponding to 20-47% of total calories from fat. Thereafter, increasing amounts of sucrose (16, 32, and 50%) and fructose (50%) were added to the 24% fat diet corresponding to 13-40% of total calories from sugar. In contrast to the fat diets, the 32% and 50% sucrose diets as well as the 50% fructose diets increased (P < 0.05) blood pressure (systolic maximum +13 mmHg, diastolic maximum +4 mmHg, mean maximum +7 mmHg) and heart rate (maximum +50 beats/min) irrespective of the day-night cycle and the unaltered locomotor activity. Furthermore, body weight increased (P < 0.05) during the 32% and 50% sucrose feedings. The increased blood pressure and heart rate normalized after rats were fed a regular chow. We concluded that an excessive caloric intake results in hyperkinetic hypertension that increases the myosin V(1) proportion.
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PMID:Radiotelemetric characterization of overweight-associated rises in blood pressure and heart rate. 1051 93


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