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

Increased vascular sensitivity to catecholamines characterizes mineralocorticoid hypertension. The present study investigated three possible sites that may account for this abnormality: agonist affinity, Ca2+ release from intracellular stores, and Ca2+ sensitivity of the contractile proteins. Adult male Sprague-Dawley rats underwent uninephrectomy and were implanted subcutaneously with deoxycorticosterone acetate (DOCA; 200 mg/kg, 1% NaCl:0.2% KCl drinking water, 4-6 weeks). Control rats were sham treated. Helical strips of mesenteric arteries were placed in muscle baths for measurement of isometric force development. Although the ED50 for norepinephrine was significantly lower in arteries from DOCA rats (pD2, 8.21 +/- 0.15) than in those from sham controls (pD2, 7.24 +/- 0.11), agonist affinity, determined by partial blockade with phenoxybenzamine, did not differ between the two groups. In contrast, norepinephrine-stimulated 45Ca2+ efflux in the absence of extracellular Ca2+ was significantly greater in arteries from DOCA rats than in those from sham rats. In the presence of ryanodine to deplete intracellular Ca2+ stores, force development to Ca2+ was not different in saponin-permeabilized vessels from DOCA rats, indicating that the Ca2+ sensitivity of the contractile proteins was not altered in DOCA hypertension. We conclude that increased vascular sensitivity to norepinephrine in mineralocorticoid hypertension is related to increased release of Ca2+ from a subcellular store and not to changes in agonist affinity or to the contractile protein interaction. Based on previous reports, it is likely that this abnormality reflects a postreceptor change in signal transduction, but there is also evidence to suggest that an increase in the number of alpha-adrenergic receptors may be involved.
Hypertension 1992 Jun
PMID:Alpha-adrenergic receptors and 45Ca2+ efflux in arteries from deoxycorticosterone acetate hypertensive rats. 131 54

Morphometric studies conducted on the blood vessels of the spontaneously hypertensive rat have provided evidence that medial hypertrophy is a key characteristic of the vascular change which occurs in hypertension. In the present study, we determined whether 3-methylhistidine (3MH), a post-translationally modified amino acid which is found uniquely in the actin and myosin of muscle, could provide a biochemical marker of such change. Our results indicated that the concentrations of 3MH were selectively elevated in the blood vessels from the spontaneously hypertensive rat, when compared with concentrations in vascular tissues from the Wistar-Kyoto rat. The concentrations of 3MH in non-vascular tissues were similar in the two strains. Chronic captopril treatment prevented the development of hypertension in the spontaneously hypertensive rat and was associated with a reduction of the vascular concentrations of 3MH. We therefore conclude that blood vessel concentrations of 3MH are a useful biochemical index of the changes in vascular smooth muscle contractile protein which occur during the development of hypertension in the spontaneously hypertensive rat.
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PMID:Chronic captopril treatment reverses the enhanced vascular concentrations of 3-methylhistidine in the spontaneously hypertensive rat. 178 98

The vessel wall is thicker in hypertension. Folkow demonstrated that adaptive structural changes occur in vessels in response to the increased wall stress of hypertension. Because the vessel wall thickens and encroaches on the lumen, the adaptive change results in an elevated vascular resistance. It also exaggerates the vasoconstrictor effects of vascular smooth muscle contraction, thereby increasing vascular reactivity to physiologically occurring vasoactive agents. As solid as this information may be, important unanswered questions still remain related to the question "What makes the pressure go up in the first place?" In this brief review, we have examined possible culprits both in the area of extrinsic vascular regulatory systems and in that of intrinsic changes in the vascular smooth muscle cell. Interesting newly described vasoactive agents currently are being evaluated. On the other hand, generalized intrinsic abnormalities in the cell membrane are well documented in hypertension. Many individual transport systems display this abnormality, suggesting that the primary defect may be in the lipid bilayer that influences the function of all integral protein transport systems. Abnormalities also have been found in the cells' signal transduction systems, whereas the energy metabolism and contractile protein system are essentially normal. Functional abnormalities of the vascular smooth muscle cell in hypertension must explain both its increased contraction and its increased growth. It is likely that the same functional abnormality may explain both of these changes.
Hypertension 1991 Nov
PMID:Pathophysiology of the vasculature in hypertension. 193 88

The purpose of this article was to review the clinical and experimental features of diabetic cardiomyopathy, with particular relevance to the Black population. One hundred thirty-seven studies were identified, of which 57 were selected as references for this article. Diabetes is associated with the development of cardiomyopathy, independent of coronary atherosclerosis. Pathological studies show myocardial hypertrophy and fibrosis; microvascular pathology is also present, but all of these pathological findings have an uncertain relationship to myocardial failure. Hemodynamic findings of both congestive and restrictive cardiomyopathy have been described. Noninvasive studies revealed abnormal systolic and diastolic function in many diabetic subjects, particularly in the presence of diabetic complications and/or hypertension. Experimental studies have focused on the mildly diabetic dog and the severely diabetic rat. One year of diabetes in dogs resulted in decreased left ventricular compliance and increased interstitial connective tissue. Studies in the diabetic rat showed a marked slowing of contraction and relaxation. Chronic insulin therapy reversed the changes in the rat model. Combining hypertension with diabetes in the rat resulted in increased myocardial and coronary microvascular pathology and greater changes in isolated muscle function, electrophysiology, and contractile protein biochemistry. Many hypertensive diabetic rats died spontaneously, showing signs of congestive heart failure. Diabetic cardiomyopathy is a significant cause of heart failure in diabetic subjects and occurs more frequently in those with microvascular complications and/or hypertension. Clinical studies are needed to clarify the natural history of this disorder, focusing on the benefits of tight control of hyperglycemia and treatment of associated hypertension. Experimental studies will clarify the pathophysiology and contribute to improved therapy. The high prevalence of diabetes and hypertension in Blacks makes these considerations especially relevant to this population.
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PMID:Diabetic cardiomyopathy. 226 38

1. Calpains (calcium-activated cysteine proteinases) have evolved by gene fusion events involving calmodulin-like genes, cysteine proteinase genes and other sequences of unknown origin. 2. The enzymes are composed of two non-identical subunits, each of which contains functional calcium-binding sequences. 3. Calpains are inhibited by the endogenous protein inhibitor, calpastatin and some calmodulin antagonists are also inhibitors of calpain. A number of synthetic proteinase inhibitors also inhibit calpains. 4. Calpains can be activated by phospholipids, an endogenous protein activator and some amino acid derivatives. 5. Various protein substrates for calpains have been recognized in vitro, but the identity of in situ substrates remains unclear. 6. Proposals have been made for calpain function, including involvement in signal transduction, platelet activation, cell fusion, mitosis and cytoskeleton and contractile protein turnover. 7. Calpain and calpastatin expression is altered in a number of abnormal states including muscular dystrophy, muscle denervation and tenotomy, hypertension and platelet abnormalities.
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PMID:Calpains (intracellular calcium-activated cysteine proteinases): structure-activity relationships and involvement in normal and abnormal cellular metabolism. 227 16

In experimental informational neurosis, accompanied by the development of stable arterial hypertension, tachycardia and dystrophic alterations in myocardium, the contractile protein ability to generate force and produce work as well as the power of the contractile process are significantly decreased and so is the intensity of Ca2+ transport through membranes of sarcoplasmic reticulum and mitochondria. Ca2+ content in these structures and energetic supply to the cardiac muscle do not change as compared with the control. Noradrenaline content in myocardium increases 5-fold compared with the control and 2.5-fold compared with the norm, while blood content falls to zero (sympathetic neuro-muscular contact is 'locked up' for noradrenaline outflow into the blood); dopamine content increases. Adenylate cyclase sensitivity to the stimulating effect of noradrenaline and NaF diminishes. Basal activity of phosphodiesterase increases, and its sensitivity to the inhibitory action of high calcium concentrations decreases. The disturbance in these systems may, on the one hand, be due to neural effects, and pressure overload of the heart, on the other hand, to the sharp rise in noradrenaline content in the myocardium and the change in the activity of cyclic adenosine monophosphate enzymes. It is suggested that similar changes may take place in the human myocardium and may underlie the cardiac weakness.
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PMID:Subcellular bases of cardiac disturbance in experimental informational neurosis. 243 90

In this article we will examine the potential impact of molecular biology on hypertension research. We will review the available molecular techniques, which include gene cloning, transient and stable expressions, as well as the use of transgenic animals. To facilitate our discussion, we will focus primarily on research of the renin gene. Renin provides a useful model that illustrates the power of biotechnology in providing detailed structural and biochemical information on a complex protein that exists in low quantities in vivo. Studies of its messenger RNA and gene expression have resulted in an improved understanding of the biology of the renin system and in generating new hypotheses. These approaches can be generalized to studies of other vasoactive hormones, contractile protein, and other gene products related to cardiovascular regulation. To elucidate the role of a specific gene in genetic hypertension, we will discuss the use of genetic markers in cosegregation or linkage analysis. Finally, we will examine the potential of transgenic animals in the study of regulation of gene expression in the whole animal and the contribution of selective genes to hypertension. We believe that molecular biology complements the biochemical and physiological approaches and provides new opportunities for furthering our concept of hypertension mechanisms.
Hypertension 1989 Jun
PMID:Role of molecular biology in hypertension research. State of the Art lecture. 266 28

We have reviewed studies of the role played by abnormalities of vascular smooth muscle in hypertension. The basic contractile apparatus of this muscle appears to be qualitatively normal, but the synthetic function of the cell is exaggerated so that more contractile protein is produced. Activation pathways of the smooth muscle cell, initiated by phospholipase C, are enhanced. A reduced ability of the endothelium to produce vascular smooth muscle relaxation may contribute to an enhanced contraction of this muscle in hypertension. Furthermore, the intrinsic cellular mechanisms that produce relaxation of this muscle may also be impaired in hypertension. However, the many abnormalities observed in membrane transport systems in this muscle in hypertension suggest that the primary defect in the cell may be a lack of stability in the membrane caused by an impairment in its ability to bind calcium.
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PMID:Vascular smooth muscle in hypertension. 268 88

The effects of renovascular hypertension on the biochemical, contractile, and electrical performance of myocardial tissue from rats of various ages has been examined. Male Fischer rats, 2, 7, 12, and 17 months old, were made hypertensive by constriction of the left renal artery. Ten weeks after the onset of hypertension, left ventricular papillary muscles were isolated from those four groups when 5, 10, 15, and 20 months old, respectively. Mechanical performance and transmembrane electrical events were recorded simultaneously. Contractile protein enzyme activity was determined in the same hearts from which papillary muscles were used for acquisition of mechanical and electrical information. There was a slight increase in blood pressure in control groups as a function of age while blood pressure maintained a range of approximately 179-188 mm Hg for all hypertensive groups. Heart weight of control animals increased significantly from 5 months to 20 months of age from 539 +/- 26 to 1088 +/- 56 mg, representing an increase of 101%. In hypertensive animals, heart weight increased 50% in 5-month-, 15% in 10-month-, 50% in 15-month-, and 11.7% in 20-month-old animals. Although control groups revealed alterations in mechanical, electrical, and biochemical parameters that increased as a function of age, the magnitude of the biochemical, contractile, and electrical response to hypertension varied monotonically with the extent of myocardial hypertrophy, rather than age per se. Adaptation to the stress of hypertension was observed in each age group, and was revealed as prolongation of mechanical and electrical timing parameters, depression of the load-velocity relation, and contractile protein enzyme activity. Thus, the stress of hypertension, which was tolerated by the 10- and 20-month-old animals with lesser relative hypertrophy and lesser changes in measured parameters, may represent a differential adaptation to the stress of hypertension.
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PMID:Myocardial biochemical, contractile, and electrical performance after imposition of hypertension in young and old rats. 293 44

Male spontaneously hypertensive rats (SHR) and age matched Wistar Kyoto normotensive (WKY) rats of 5 weeks, 16 weeks, and 52 weeks of age were used to determine whether duration of hypertension has any effect on contractile protein ATPase and myosin isoenzyme distribution. Myofibrils, actomyosin, and myosin were isolated from the left ventricles of WKY rats and SHR and assayed for myosin ATPase activity and myosin isoenzyme distribution. Myofibrillar ATPase activity was assayed at various free [Ca++] ranging from 10(-7) to 10(-5) mol X litre-1. Ca++ stimulated actomyosin ATPase activity was determined at several Ca++ concentrations both at low ionic strength, which favours actin-myosin interaction, and at high ionic strength, which diminishes actin interaction with myosin. Purified myosin ATPase activity was assayed in the presence of K+-EDTA and in the presence of several concentrations of Ca++. Actin activated myosin ATPase activity was assayed using 26 mumol X litre-1 skeletal muscle actin. Under all these assay conditions no differences were observed in the contractile protein ATPase activity between SHR and WKY rats in any age group. On the other hand, in both SHR and WKY rats the contractile protein ATPase activity under all assay conditions was significantly decreased in 52 week old rats compared with 5 week old rats. The predominant myosin isoenzyme was Vi in 5 week and 16 week old WKY rats and SHR. In 52 week old WKY rats and SHR, however, significant amounts of isoenzymes V2 and V3 were present along with V1. Percentage distribution of V1, V2, V3 isoenzymes calculated from densitometric scans of gels did not show any differences between WKY rats and SHR in any age group. These results suggest that neither myosin ATPase activity nor myosin isoenzyme distribution is altered in the moderately hypertrophied left ventricles of SHR. Moreover, the data indicate that the myocardium of SHR, despite the persistence of pressure overload, undergoes a similar decrease in myosin ATPase activity and an increase in myosin isoenzyme V3 to age matched normotensive WKY rats.
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PMID:Age dependent changes in myosin ATPase activity in the myocardium of spontaneously hypertensive rats. 293 54


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