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)

Two distinct myosin heavy chain isoforms, referred to as alpha and beta, were identified in the human heart with specific antimyosin antibodies. By indirect immunofluorescence, myosin heavy chain alpha was found to be a major component of atrial myosin and a minor component of ventricular myosin, while heavy chain beta was found to be a major component of ventricular myosin and a minor component of atrial myosin. In the normal heart, there was marked individual variability in the proportion of ventricular myocytes reactive for heavy chain alpha. Atrial myocytes staining for heavy chain beta were rare in the left atrium and more numerous in the right atrium, especially in the crista terminalis and in the interatrial septum. Surgical and autoptic specimens from hypertrophied left ventricles of patients with mitral regurgitation showed a myosin immunoreactivity pattern similar to that of normal specimens. Very rare muscle cells reactive for heavy chain alpha were seen in the hypertrophied left ventricles of subjects with hypertension and in the hypertrophied right ventricles of subjects with tetralogy of Fallot. A dramatic transformation of myosin heavy chain composition was observed in hypertrophied left atria of patients with mitral stenosis, with a shift to heavy chain beta in a large proportion of atrial myocytes. The findings indicate that chronic exposure to hemodynamic overload can induce marked changes in the myosin heavy chain composition of human atria, whereas it affects only slightly that of the ventricles.
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PMID:Myosin types in the human heart. An immunofluorescence study of normal and hypertrophied atrial and ventricular myocardium. 623 8

Myocardial hypertrophy, with high morbidity and mortality, is a natural outcome of hypertensive heart disease. The increase in myocardial mass is associated with a cellular and subcellular reorganization of the myocytes. The following study uses rapid myothermal techniques to assess the contribution of the major intracellular changes to the adaptive hypertrophic process in various heart models. Pressure overload and thyrotoxic hypertrophy were produced in the rabbit. In the rat, hypertrophy was produced by constricting the renal artery (Goldblatt hypertensive rat) or by using the spontaneously hypertensive rat strain. Atrophy was produced by administration of propylthiouracil in the drinking water. The V1/V3 myosin isoenzyme ratio was decreased in the pressure overload, Goldblatt, and propylthiouracil animals. This was associated with a decrease in total activity-related heat, initial heat, and tension-dependent heat per tension time integral. The tension-independent heat was decreased in the pressure overload, while the time to peak tension was increased. The economy of the metabolic recovery process was unchanged in the pressure overload and Goldblatt preparations. In the propylthiouracil preparation the recovery processes became uneconomical. The spontaneously hypertensive rat exhibited mild cardiac hypertrophy but in all other respects the heart was unchanged from the normal animals. The thyrotoxic hearts had a high V1/V3 myosin isoenzyme ratio, which was associated with a high total activity-related heat, initial heat, and tension-dependent heat per tension time integral. The tension-independent heat was reduced in the thyrotoxic preparations. The appropriateness of each of the intracellular changes is evaluated in terms of the demands made on the heart.
Hypertension
PMID:The inhomogeneity and appropriateness of the myocardial response to stress. 624 Apr 54

Two antigenically distinct types of myosin heavy chain, referred to as alpha and beta, have been identified in autoptic and bioptic specimens of human heart using specific antimyosin antibodies. By immunofluorescence heavy chain alpha was present in all atrial myocytes and in a variable number of ventricular myocytes. Heavy chain beta was present in all ventricular myocytes and in a number of atrial myocytes. Ventricular hypertrophy in patients with aortic stenosis, systemic hypertension or tetralogy of Fallot was characterized by an almost complete absence of fibres reactive with anti-alpha. A striking decrease in alpha chain reactivity and a parallel increase in beta chain reactivity was apparent in the hypertrophied left atria of patients with mitral stenosis. To quantify these myosin changes a novel procedure was developed whereby myosin was extracted from single cryosections serial to those processed for immunofluorescence and the relative amount of alpha and beta heavy chain was determined by enzyme immunoassay. Heavy chain alpha was less than 5% in most normal ventricular specimens and disappeared completely under the effect of pressure overload. On the other hand heavy chain beta was generally undetectable in the left atrial myocardium but increased up to 90% in biopsies of hypertrophied atria.
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PMID:Myosin changes in hypertrophied human atrial and ventricular myocardium. A correlated immunofluorescence and quantitative immunochemical study on serial cryosections. 624 7

We have used affinity-purified antibodies reacting with guinea pig soleus muscle and ventricular myosin heavy chains to analyze the distribution of specific isomyosin in the ventricular myocardium of normal and renal hypertensive rats. Immunofluorescent staining of cardiac tissue sections with the two antimyosins revealed striking variations in reactivity among ventricular muscle fibers, reactive fibers being more numerous in the left compared to the right ventricle and in subendocardial compared to subepicardial layers. The response of the ventricular myocardium changed during development: all fibers were stained in the newborn rat, whereas most fibers were unreactive in 1-month-old animals. The number of reactive fibers increased again in subsequent stages leading to a mixed pattern in adult animals. The normal mixed pattern of reactivity was transformed into a uniformly positive pattern in hypertensive rats 2 months after surgery. This complete transformation was observed in 20 out of 23 hypertensive animals examined. These findings indicate that the two antimyosins cross-react with a particular type of ventricular myosin heavy chain, whose distribution varies in different muscle cells and whose relative concentration changes during development and during cardiac hypertrophy induced by systemic hypertension. We suggest that differences in pressure load may be responsible for both regional variations in isomyosin distribution and for isomyosin changes in hypertensive animals.
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PMID:Isomyosin distribution in normal and pressure-overloaded rat ventricular myocardium. An immunohistochemical study. 645 85

Microchemical techniques were employed to measure the DNA, contractile proteins, and connective tissue protein composition of 150 micrograms samples of mesenteric and cerebral resistance arteries taken from 25-week-old spontaneously hypertensive (SHR) and control Wistar-Kyoto (WKY) rats. The active and passive mechanical properties of intact resistance arteries also were determined. The DNA content of branches of the posterior cerebral and mesenteric arteries (170 micrometers I.D.) were elevated by nearly 30% in the SHR compared to the WKY. The amounts of actin and myosin when normalized to DNA content were unchanged in SHR mesenteric arteries compared to control, whereas these amounts were decreased by 25% and 49%, respectively, in the SHR cerebral arteries vs control. The functional implications of these contractile protein measurements agreed with determinations of active smooth muscle cell stress-generating capabilities, which were found unchanged in the mesenteric arteries and depressed in the SHR cerebral arteries. Neither the absolute amounts and concentrations (relative to tissue mass) of elastin in mesenteric and cerebral arteries, nor the absolute amounts and concentrations of collagen in the mesenteric artery, were changed in the SHR. However, cerebral artery total collagen was elevated by 31% in the SHR, with no change in collagen concentration between the two strains. Under conditions where the smooth muscle cells were fully relaxed, the internal radii of SHR brain and SHR mesenteric arteries were smaller at all pressures with respect to the WKY. However, only the SHR cerebral arteries were actually less distensible than controls. Thus, it is apparent that hypertension-associated changes in the chemical and mechanical properties of the resistance artery wall vary considerably depending upon which vascular bed is examined. The measurements made in this study suggest that these changes are more pronounced in brain arteries. This finding could be of significance regarding the autoregulatory capability of, and blood pressure distribution within, brain vessels of hypertensive animals.
Hypertension
PMID:Biochemical and mechanical properties of resistance arteries from normotensive and hypertensive rats. 684 64

The goal of this study was to characterize the influence of low protein diet on vascular changes induced by deoxycorticosterone acetate (DOCA) hypertension. DOCA hypertensive and control normotensive rats were placed on a low protein (5%) diet for 4 weeks. This intervention blocked the further increase in systolic blood pressure of rats treated with DOCA; systolic blood pressures of control rats were not influenced by the low protein diet. The sensitivity of isolated mesenteric arteries to norepinephrine was increased in DOCA hypertensive rats compared to that in arteries from control rats; arterial strips from rats maintained on the low protein diet were less sensitive to the catecholamine than arteries from their respective control diet group. Vascular sensitivity to calcium was identical in both normotensive and DOCA hypertensive rats, and the low protein diet had no effect on this measure of calcium activation. Calcium-induced relaxation was depressed in arteries from DOCA hypertensive rats, suggesting a decreased stabilizing influence of the cation on the excitable membrane. Arteries from rats maintained on the low protein diet showed enhanced relaxation to calcium compared to those from their respective control diet group. Membrane stores of calcium available for activation by norepinephrine were increased in arteries from DOCA hypertensive rats; the low protein diet decreased the storage capacity of these membrane sites. The total protein content of the aorta was increased in DOCA hypertensive rats and depressed to control level in DOCA rats maintained on low protein diet. No change was observed in actomyosin content nor in the actin-to-myosin ratio during the DOCA hypertension or the addition of a low protein diet. Since one action of DOCA is to increase cellular protein synthesis, the attenuation of these vascular changes in DOCA rats maintained on a protein-deficient diet is probably due to a decrease in available substrate.
Hypertension
PMID:Vascular changes in DOCA hypertension. Influence of a low protein diet. 710 53

We report the ultrastructure of bilateral renal angiomyolipomas in a case of tuberous sclerosis. The patient also had adult-type polycystic renal disease (Potter type 3) with systemic hypertension. Smooth muscle differentiation was supported by immunofluorescence localization of contractile protein using both smooth muscle and platelet-specific antibodies against myosin. There were cells with ultrastructural features intermediate between mature smooth muscle and fat suggesting origin from progenitor pericytic cells closely related to vascular endothelium. There was also evidence of secretory or synthetic capacity by some mesenchymal cells raising the possibility that hypertension in part may have been hormonally mediated by tumor. A unifying theory of histogenesis is proposed with special reference to the study of Wassermann regarding embryonal lipogenesis.
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PMID:Angiomyolipomas and polycystic renal disease in tuberous sclerosis. Ultrastructural observations. 724 58

We examined the interaction among changes in pHi, [Ca2+]i, myosin light-chain phosphorylation, and contraction in arterial smooth muscle stimulated by histamine, NH4+, Tris+, and/or changes in extracellular pH (pHo). We loaded swine carotid medial tissues with 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein to measure pHi or aequorin to measure [Ca2+]i. Incubation of tissues in NH4+ increased pHi, [Ca2+]i, myosin phosphorylation, and force. Washout of NH4+ decreased pHi and transiently further increased in [Ca2+]i and force. Incubation of tissues in a similar concentration of Tris+ or increasing pHo also increased pHi; however, there were only modest changes in [Ca2+]i and force. Increasing extracellular pH coincidentally with washout of NH4+ prevented the decrease in pHi but did not affect the NH4+ washout-induced contraction. These data suggest that NH4+ altered [Ca2+]i and contraction by mechanisms other than its effects on pHi. The type of pH buffer did not affect the [Ca2+]i, myosin phosphorylation, or stress response to histamine stimulation. The time course of changes in pHi was much slower than the time course of histamine-induced changes in [Ca2+]i, myosin phosphorylation, and stress. Addition of 10 mmol/L NH4+ concurrently with histamine aborted the histamine-induced decrease in pHi and significantly slowed the histamine-induced increase in [Ca2+]i, myosin phosphorylation, and stress. There was little effect on histamine-induced increases in [Ca2+]i, myosin phosphorylation, or contraction when three other protocols aborted the histamine-induced decrease in pHi. These data show that incubation in NH4+ can alter [Ca2+]i and contraction in both unstimulated and histamine-stimulated smooth muscle. However, these effects were not caused by NH4(+)-dependent changes in pHi.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:pHi, [Ca2+]i, and myosin phosphorylation in histamine- and NH4(+)-induced swine carotid artery contraction. 772 87

Experimental hypertension can be induced in rats by uninephrectomy, administration of deoxycorticosterone acetate (DOCA) and sodium chloride. We developed this model in the guinea pig, because it presents an isoenzymic myosin pattern and calcium-induced calcium release similar to those of humans. Unilateral nephrectomy was performed in 33 guinea pigs, after which they were given DOCA (300 mg/kg pellets, s.c.; n = 11, or 10 mg, i.m.; n = 12, 5 days a week for 5 weeks). One week after surgery, drinking water was supplemented with NaCl 9 g/l and KCl 2 g/l for 5 weeks. Control guinea pigs (n = 10) were nephrectomized but not treated. Five weeks after surgery, hemodynamic measurements were recorded and the animals sacrificed to assess the degree of left ventricular hypertrophy. Left ventricular hypertrophy was considered significant if the ratio of left ventricular weight/body weight was > 2.3 and if the thickness of the left ventricle free wall was > 3.5 mm. Results showed that the systolic, diastolic and mean blood pressures of the treated groups were 36% higher than in the control group. Cardiac hypertrophy occurred within 5 weeks, and resulted in an increase in left ventricle weight and in left ventricular hypertrophy. The possibility of using the DOCA salt model of experimental hypertension in the guinea pig could help to elucidate the mechanisms responsible for hypertension and induced left ventricular hypertrophy, and thus improve prevention and treatment.
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PMID:Induction of hypertension and cardiac hypertrophy in guinea pig by DOCA salt. 783 30

In this review we have analyzed the present knowledge about the differentiation and growth processes in vascular smooth muscle cells (SMC) in hypertension. The study of smooth muscle (SM) and nonmuscle (NM) myosin isoform expression has permitted us to identify a three-stage specific maturational pathway, namely, fetal, postnatal, and adult. In the renovascular (rabbit) and genetic (rat) models of hypertension, adaptive changes occurring in hypertensive vessels make SMC resemble those found in the early stages of development (smooth muscle plasticity). In fact, based on SM- and NM-myosin isoform distribution, postnatal-type SMC predominate in the arterial media during the early remodeling of the arterial wall that occurs in hypertension, whereas postnatal- and fetal-type SMC predominate in the intimal thickening. Locally produced or activated autocrine/paracrine factors, such as growth factors or cytokines, along with circulating hormones, seem to be involved in the growth response or changes in the differentiation pattern of SMC. Thus, these factors not only play a specific role in the regulation of blood pressure, but also are likely to be responsible for the remodeling of the arterial wall in hypertension.
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PMID:Differentiation and growth of vascular smooth muscle cells in experimental hypertension. 794 70


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