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

The cardiac changes resulting from mechanical overload of the left ventricle have been well documented and a variety of compensatory mechanisms described. These include a decrease in maximum velocity (V0) of shortening in the absence of reduction in active tension (P0), and a reversible decrease in myofibrillar adenosine triphosphatase activity resulting from isoenzymic shift from, predominantly, a form of myosin with high ATPase activity (V1) to another with low (V3). The thermodynamic advantage of the transition is the hypertrophied muscle possesses a more energy-efficient form of contraction. These reversible transitions resulted from altered gene expression of isoenzymic forms of myosin heavy chain. It must be borne in mind that the adaptational modifications just described appear to occur only in smaller animals such as the rat, that possesses several myosin isozymes. In large mammals it is mainly the V3 form of myosin that is present, which does not change with altered contractile state. Responses of the large arteries to hypertension have been poorly studied. This is surprising when one recalls that degenerative disease of such vessels, that include the aorta, carotids and ileo-femoral arteries is almost an obligatory concomitant of hypertension. Such studies as have been carried out indicate that hyperplasia is specific for abdominal aortic stenosis while hypertrophy is found in aortic smooth muscle in rats with systemic hypertension. Mechanically, an increase in V0 with no change in P0 have been reported; an increase in myofibrillar ATPase activity was also reported. Though two myosin heavy chain isozymes have been found in aortic smooth muscle densitometry did not reveal any difference in distribution between tissues from control and hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cardiovascular adaptations to mechanical overload. 213 92

Heart myosin isoforms and arterial blood pressure changes were studied in 30 SHR rats following a long-term treatment with captopril. 30 Wistar rats were included in the same trial as control. Twelve week old SHR rats with an already established hypertension and ventricular hypertrophy were orally administered with between 25 and 100 mg/Kg/die of captopril. After a ten-week treatment, animals were sacrificed and heart myosin isoforms (V1, V2, V3) analysed by polyacrylamide gel electrophoresis. Our results showed that captopril can: a) reduce blood pressure; b) reduce the cardiac hypertrophy; c) reverse the isomyosin enzymes (V1 V3) previously altered by the hypertrophy condition (V3 V1) to normal value. Furthermore we have detected an increase of V myosin isoform in SHR rats (35%) and to a lower extent in treated Wistar rats (17%). Since SHR and Wistar rats usually do not express V isoform, our results suggest that captopril may be responsible for this phenomenon by acting directly on myocardial cells.
 ...
PMID:[Effects of long-term treatment with captopril on the isomyosin profile of the heart from SHR and Wistar rats]. 214 74

Previous studies have demonstrated a role for sex hormones in maintaining normal heart weight and myosin isoenzyme balance in the rat. To determine if sex hormones were necessary to elicit cardiac adaptations to the chronic loads of swimming or hypertension, female rats were gonadectomized (X) and then exposed either to a chronic swimming program (Sw) or to renal hypertension for 8-10 wk. Because gonadectomy in females increased heart and body weight, separate groups of food-restricted sedentary and Sw gonadectomized females (XFR) were included. Swimming resulted in significant increases in both heart weight and in the percent ventricular V1 isomyosin in female controls (C), X, and XFR. Hypertension was studied in C, X, and X with estrogen replacement. Cardiac hypertrophy developed in all groups, but estrogen therapy attenuated the decline in percent V1 isomyosin in both normotensive and hypertensive X animals. Swimming, which is generally not associated with cardiac hypertrophy in males, was also studied in that sex. Gonadectomy did not alter either the heart weight or the myosin isoenzyme response to Sw, although testosterone replacement in gonadectomized males restored ventricular V1 myosin levels to or above normal. Measures of serum thyroid levels and of myocardial catecholamines failed to demonstrate a causal relationship between these hormones and the various results. Therefore, although sex hormones are important for maintaining normal heart weights and myosin isoenzyme balance in rats, they do not appear to be important in the adaptations hearts exhibit when exposed to physiological or pathological loads.
 ...
PMID:Effects of sex hormones on development of physiological and pathological cardiac hypertrophy in male and female rats. 214 4

Several experimental models involving the development of cardiac hypertrophy in adult rats are characterized by the reexpression of the fetal isoform of myosin heavy chain (V3). To determine whether a similar adult-to-fetal shift in the expression of the thin-filament proteins occurs during cardiac hypertrophy, we have examined the expression of the isoforms of myosin, tropomyosin, and troponin T in the left ventricle of young spontaneously hypertensive rats (SHR) with and without treatment using enalapril, an angiotensin converting enzyme inhibitor. Phosphorylation of tropomyosin, which is predominant in the fetal state, was also analyzed. Twelve-week-old SHR were treated with enalapril for 2, 5, 8, and 9 weeks followed by withdrawal of treatment for 9 weeks. Control SHR, without drug treatment, were weight- and age-matched. After 9 weeks of enalapril treatment, mean arterial blood pressure was reduced (from 166 +/- 11 to 89 +/- 5 mm Hg), and left ventricular weight/body weight ratio was regressed (from 2.53 +/- 0.14 to 1.96 +/- 0.05 g/kg) to normotensive levels. During the 9-week treatment period, the percent V3 decreased in SHR substantially from 35 +/- 3% to 13 +/- 1%. There was a significant correlation between the left ventricular hypertrophy and the percent V3 myosin expression in the SHR during regression (r = 0.697, p less than 0.001). However, only the adult isoforms of tropomyosin and troponin T were detected in the SHR with or without enalapril treatment, and the level of tropomyosin phosphorylation remained constant irrespective of the degree of left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Dec
PMID:Regression of cardiac hypertrophy in spontaneously hypertensive rats by enalapril and the expression of contractile proteins. 214 74

Sustained smooth muscle contraction has been proposed to be regulated by either 1) sustained increases in intracellular Ca2+ concentration [(Ca2+]i)-dependent myosin phosphorylation or 2) diacylglycerol-dependent protein kinase C activation. We measured diacylglycerol mass with the diacylglycerol kinase assay and myoplasmic [Ca2+] with aequorin in swine carotid medial smooth muscle. Sustained and significant increases in [Ca2+], myosin light chain phosphorylation, and isometric stress were observed with histamine or endothelin stimulation. Neither stimuli, however, induced significant increases in diacylglycerol mass. Relaxation of histamine-stimulated tissues was induced by removal of histamine or removal of extracellular CaCl2 in the continued presence of histamine. The rate of decline of both [Ca2+] and force was similar in both protocols, suggesting that removal of Ca2+ (without removing the stimulus) was equivalent to removal of the stimulus. These data suggest that [Ca2+]i is the primary regulator of sustained swine arterial smooth muscle contraction, whereas diacylglycerol has, at most, only a minor role.
Hypertension 1990 Jun
PMID:[Ca2+], not diacylglycerol, is the primary regulator of sustained swine arterial smooth muscle contraction. 219 Sep 21

The Ca2+, calmodulin (CaM)-dependent phosphorylation of the 20 kDa myosin light chain (LC20) is accepted as an important component of the regulatory mechanism in smooth muscle contraction. Since we have originally developed selective inhibitors of each process of the intracellular Ca2+ messenger system, the effect of a newly synthesized compound ML-9, a myosin light chain kinase (MLCK) inhibitor on superprecipitation of actomyosin, isometric tension development and phosphorylation of LC20 in vascular smooth muscle was investigated. Superprecipitation of actomyosin from bovine aorta was inhibited by the addition of ML-9 in a dose-dependent manner. In chemically skinned smooth muscle cells of the rabbit mesenteric artery, ML-9 inhibited both Ca2+ and Ca2+, CaM-independent MLCK-induced contraction. In the intact vascular strips, increase in LC20 phosphorylation reached a maximal value within 10 sec from a resting value, and then declined to near the basal level during the maintained isometric force developed in response to 50 mmol/L KCl. Both the maximal rate and extent of KCl-induced contraction and the phosphorylation of LC20 were also inhibited by ML-9. It antagonized the contraction induced by various contractile agonists, such as NE, 5HT, His, and Ang II concomitant with the inhibition of LC20 phosphorylation. These results suggest that ML-9 inhibits the actin-myosin interaction through the modulation of LC20 phosphorylation via the inhibition of MLCK activity. ML-9 will aid in determining pathophysiological functions of MLCK of increased vascular contractility in hypertension.
 ...
PMID:Molecular pharmacology of calcium, calmodulin-dependent myosin phosphorylation in vascular smooth muscle. 222 74

The relative proportion of the two putative heavy chains of smooth muscle myosin (MHC1 and MHC2) was determined in the caudal and femoral arteries of spontaneously hypertensive rats (SHR) and normotensive (WKY) rats at 16 weeks of age. The heavy chain polypeptides with Mr 204,000 and 200,000 were resolved electrophoretically under denaturing conditions in porous polyacrylamide gels. Both proteins reacted strongly with a monoclonal antibody (2C4) to smooth muscle MHC. In caudal arteries the ratio of MHC1/MHC2 was 3.1:1 in SHR rats compared with 1.8:1 in WKY rats (p less than 0.005) and similarly in femoral arteries, 2.8:1 vs 1.5:1 (p less than 0.001). In the portal vein there was no significant difference, 1.7:1 vs 1.5:1. The possibility that the higher MHC ratio in the SHR is the genetically mediated defect in arterial smooth muscle cells leading to the hypertension is discussed as an alternative to the elevated systemic blood pressure causing the altered MHC ratio.
 ...
PMID:Different ratio of myosin heavy chain isoforms in arterial smooth muscle of spontaneously hypertensive rats. 235 Mar 34

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used to investigate the adaptive biochemical changes in the myocardium in response to chronic afterload. Ouabain-inhibited Na+,K+-adenosine triphosphatase (ATPase) activity was decreased by 40% in myocardium of SHR compared with that from WKY, which may lead to increased intracellular Ca2+ through Na+-Ca2+ exchange. Similarly, alpha 1-adrenergic receptor density, estimated by [3H]prazosin binding, was decreased by 42% in myocardial membranes of SHR, while the affinity for the agonist and the antagonist was not altered. In contrast, the number of Ca2+ channels estimated by [3H]nitrendipine binding was increased by 45% in myocardial membranes of SHR, while the affinity was comparable between SHR and WKY. These differences between WKY and SHR in the membrane properties were not due to differential contamination of plasma membranes because the activities of other putative plasma membrane marker enzymes were comparable between WKY and SHR. There were no differences between WKY and SHR in the myosin ATPase activity estimated using myofibrils, actomyosin, and myosin. These results suggest that specific alterations have occurred in the plasma membrane properties of myocardium of SHR that result in altered intracellular Ca2+ metabolism. These alterations may have an important bearing on excitation-contraction coupling in myocardium of SHR.
Hypertension 1986 Jul
PMID:Alterations in the plasma membrane properties of the myocardium of spontaneously hypertensive rats. 242 36

The phosphorylation hypothesis of smooth muscle contraction relates formation of cyclic AMP, resulting from beta-adrenergic stimulation, to inhibition of myosin light-chain phosphorylation and hence to bronchial relaxation. The hypothesis can therefore explain why beta-adrenergic blockade promotes bronchospasm in susceptible individuals. In the light of this molecular schema, various novel approaches to the use of beta-adrenergic blocking therapy for hypertension in the presence of asthma are discussed.
 ...
PMID:Mechanism of smooth muscle contraction: relevance to safety of beta-adrenergic blockade in hypertensive patients with reversible chronic obstructive airways disease. 242 52

The manifestations of cardiac involvement in hypertension include: (1) the development of hypertensive heart disease characterized by left ventricular hypertrophy (LVH), and (2) the consequences of coronary atherosclerosis, as angina pectoris, myocardial infarction, and sudden cardiac death. Whereas the former is directly related to increased blood pressure, the latter are sequelae of atherosclerosis per se, and hypertension acts only as a risk factor in this regard. This can partially explain why antihypertensive treatment is effective in diminishing the incidence of congestive heart failure, which is the final consequence of LVH, but is not very effective in preventing coronary complications. It is generally accepted about LVH that increased arterial pressure is the major stimulus to cardiac hypertrophy in hypertension; however, there are a lot of both quantitative and qualitative events suggesting that other factors beside blood pressure levels can modulate the development of LVH, in particular neurohumoral influences. From a morphological point of view, hypertrophy of the cardiac muscle is defined as an increase in the size of existing myocardial fibers. In most experimental models, myocardial hypertrophy is associated with myosin isoenzymatic changes, consisting in a shift from the faster migrating isoenzyme V1 to V3, a form that migrates more slowly. However these changes do not occur in all animal species and particularly in humans. In the hypertrophied human ventricle, a decreased ATPase activity of myofibrils was observed, probably related to changes in myosin light chains. Presently the changes in ATPase activity and in ventricular contractility do not still have a clear molecular basis in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Heart and hypertension. 252 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>