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)

Symptoms of dyspnea and fatigue limit effort tolerance in patients with chronic cardiac failure. These symptoms may be consequent to an abnormal cardiocirculatory response to the increased O2 demand that accompanies exercise as manifested by: reduced ability to augment cardiac output in response to increased left ventricular filling pressure, inadequate vasodilatory response in exercising limbs, the onset of lactate production by muscle at relatively low levels of work, and increased work of breathing that accompanies pulmonary venous hypertension and abnormal compliance of the lung secondary to left ventricular dysfunction. The clinical experience with new positive inotropic agents in the long-term treatment of patients with chronic cardiac failure is accumulating rapidly. Attention has focused on the ability of these agents to improve exercise performance, particularly their ability to increase the aerobic capacity. The experience to date suggest that beta-adrenergic receptor agonists offer little advantage in this regard while causing ventricular arrhythmias. On the other hand, the phosphodiesterase inhibitors, MDL 17,043 and MDL 19,205, and the bipyridine derivatives, amrinone and milrinone, may improve exercise performance in many patients and exert a sustained effect during long-term therapy. Placebo-controlled, randomized trials will need to be performed, however, to determine the ultimate efficacy and safety of these agents. The most meaningful results for analysis will be obtained when objective parameters of exercise performance, such as aerobic capacity and anaerobic threshold, are monitored that are free of patient or physician bias.
 ...
PMID:Effects of new inotropic agents on exercise performance. 286 37

Human pregnancy is characterized by a blunted pressor responsiveness to vasopressor substances. This was first reported by Dieckmann and Michel in 1937 in experiments in which they measured vascular reactivity to the pressor effects of a crude preparation of vasopressin. Recently, this has been reported to occur in response to epinephrine, norepinephrine (NE), and angiotensin II (AII). Gant and associates reported that the increasing vascular sensitivity to infused AII not only was characteristic of women who developed pregnancy-induced hypertension, but in fact preceded the development of pregnancy-induced hypertension. Although a variety of factors may mediate this blunted pressor responsiveness, the most likely candidate appears to be the localized production within endothelium and/or vascular smooth muscle of prostaglandins. Indeed, administration of indomethacin or aspirin results in an increased sensitivity to infused AII in normotensive previously AII-refractory women. Administration of the steroid hormone 5 alpha-dihydroprogesterone reverses this apparent prostaglandin-mediated response. In addition, administration of the phosphodiesterase inhibitor, theophylline, results in a restoration of vascular refractoriness to infused AII in women with pregnancy-induced hypertension or in women destined to develop pregnancy-induced hypertension. Although a variety of known and possibly unknown compounds might also effect the control of vascular reactivity during human pregnancy, the prostinoids appear to play a pivotal role in mediation of control of vascular reactivity during human pregnancy.
 ...
PMID:Control of vascular reactivity in pregnancy. 355 2

Using column chromatography with phenylcepharase, calmodulin was isolated from the brain of rats with spontaneous hypertension (SHR) and control normotensive rats (NKWR). As judged from the findings of electrophoresis in polyacrylamide gel, UV-spectroscopy and spectrofluometry, the obtained samples of calmodulin contained no significant admixture of other proteins. The Ca-binding capacity of calmodulin of the brain of SHR and NKWR estimated by the method of fluorescent probes were identical. There were also no differences in their capacity to interact with troponine I and to activate the Ca-pump of the erythrocytic membrane and phosphodiesterase of the cardiac muscle. A study on the dependence of activity of phosphodiesterase on the protein content of the brain homogenate from SHR and NKWR revealed no differences in the calmodulin levels in this tissue. On the basis of these data a conclusion was made that impairments of the intracellular distribution of calcium in primary hypertension described earlier are not related to disorders in the metabolism of the universal Ca-binding protein-regulator.
 ...
PMID:[Isolation and characteristics of calmodulin from the brains of rats with spontaneous genetic hypertension]. 398 65

In the aortas and mesenteric arteries from spontaneous hypertensive rats and in the aortas from stress- and desoxycorticosterone-acetate-hypertensive rats, the intracellular cGMP: cAMP ratios were significantly elevated when compared to the ratios in the aortas of the respective controls. Decreases in the intracellular cAMP or cGMP levels were consistently associated with increased activity of the cyclic-nucleotide-specific low K(m) phosphodiesterase (3':5'-cAMP 5' nucleotidohydrolase, EC 3.1.4.17). Increases in intracellular cGMP levels were associated with elevated guanylyl cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity. Furthermore, adenylyl cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity was less sensitive to stimulation by the beta-adrenergic stimulant isoproterenol in both the aortas and the hearts of the hypertensive animals. These changes could provide the biochemical basis for the (a) increased vascular smooth muscle tone and peripheral resistance observed in these animals, (b) increased reactivity to norepinephrine, and (c) decreased ability of aortas from hypertensive rats to relax. The presence of these same effects in different etiologic types of hypertension indicates that this aberration in cyclic nucleotide metabolism may represent a common metabolic defect basic to the hypertensive syndrome irrespective of etiology.
 ...
PMID:Aberrations of cyclic nucleotide metabolism in the hearts and vessels of hypertensive rats. 415 74

Restriction of motor activity and motor-alimentary conditioning in dogs reduced the adrenaline (A) and noradrenaline (NA) contents in the myocardium, dopamine, too, revealing a tendency to reduction. Basal activity of the sarcolemma adenylate cyclase (AC), its sensitivity to A, NA and NaF did not change as well as the basal activity of sarcolemma phosphodiesterase (PDE) and its sensitivity to the inhibitory effect of high concentrations of Ca2 (10(-4) M). In experimental informational neurosis, NA content in the myocardium increased 5-fold compared to control values, the dopamine content also increasing. Basal activity of the sarcolemma AC did not change whereas its sensitivity to NA and to activating effect of NaF decreased. Basal activity of PDE increased and its sensitivity to Ca2 effect decreased in this condition. The increase of PDE activity and increase of its sensitivity to the inhibitory effect of high concentrations of Ca2+ in combination with desensitization of the regulatory subunit AC to NA followed by changes in its catalytic subunit, seem to lead to a decrease of cAMP content and cAMP-dependent phosphorylation in cardiomyocyte that may underlie the Ca2+ transport disturbance observed in informational neurosis, and reduction of contractility of the contractile protein system. Heart pressure overload, caused in informational neurosis by the stable arterial hypertension may play an important role in the genesis of this reduction.
 ...
PMID:[Catecholamine concentration and adenyl cyclase and phosphodiesterase activities of the sarcolemma of myocardial cells during hypokinesia and in experimental information neuroses]. 609 71

Cadmium (Cd) produces injurious effects on reproductive function and has been implicated in the pathogeneses of hypertension. The present article summarizes available data on alterations in the cyclic AMP system of testicular and prostatic tissue as well as in catecholamine metabolism in adrenal glands following exposure to Cd and subsequent withdrawal. Daily Cd (1 mg/kg IP) for 45 days decreased prostatic and testicular weights of mature male rats. In prostate, chronic treatment with Cd reduced cyclic AMP levels to 57% of normal values which appeared to be due to the decrease in adenylate cyclase activity since cyclic AMP metabolism by phosphodiesterase was not significantly altered. Cyclic AMP binding to prostatic protein kinase was increased following Cd administration as was the activity of the cyclic AMP-dependent form of protein kinase. In contrast to the prostate, testicular adenylate cyclase was stimulated by Cd treatment. However, the endogenous cyclic AMP levels remained unaffected since the increase in testicular adenylate cyclase was offset by a concomitant increase in the activity of phosphodiesterase. Although the activities of the cyclic AMP-dependent and the independent forms of testicular protein kinase were significantly depressed, the binding of cyclic AMP to protein kinase from testes of Cd-treated rats was not affected. Discontinuation of treatment for 28 days in rats that had previously been given the heavy metal for 45 days resulted in at least a partial reversal of several of the cadmium-induced changes in cyclic AMP metabolism of the rat prostate and testes. However, the weight of the prostate glands remained essentially in the same range as that seen in the "treated group."Data suggest that cyclic AMP metabolism in both the primary and the secondary reproductive organs is altered following chronic Cd treatment and that some changes persist even 28 days following the termination of daily exposure to the heavy metal.Cd treatment also increased adrenal weights and augmented the levels of adrenal norepinephrine and epinephrine as well as the activity of tyrosine hydroxylase. Discontinuation of the heavy metal treatment for 28 days, in rats previously injected with Cd for 45 days, restored the activity of tyrosine hydroxylase as well as the amount of norepinephrine and epinephrine. In contrast, adrenal weights were restored only partially following withdrawal of Cd treatment. Evidence indicates that the changes in adrenal catecholamine metabolism may be the result of stress induced by chronic exposure to this heavy metal. In addition, some of the untoward effects such as hyperglycemia and arterial hypertension seen during Cd toxicity might be related to increased synthesis of epinephrine in adrenal glands.
 ...
PMID:Testicular cyclic nucleotide and adrenal catecholamine metabolism following chronic exposure to cadmium. 611 36

Adenosine 3',5'-cyclic monophosphate (cAMP) metabolism was studied in the microcirculation (100- to 150-micrometers arterioles) of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) at different stages of hypertension. Mesenteric arterioles from animals 4, 6, 12, and 18 wk old were incubated in Krebs-Ringer bicarbonate buffer for 30 min at 37 degrees C, pH 7.4, with and without the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (MIX). cAMP was assayed by radioimmunoassay. Arteriolar production of cAMP was age related in both WKY and SHR rats although the temporal patterns were different. At 6 wk (developmental stage of hypertension in SHR) cAMP accumulation in the presence or absence of MIX by SHR arterioles was higher than in the WKY before falling to normotensive levels at 12 wk. Salbutamol (a beta 2-agonist) stimulated dose-dependent increases in cAMP in both WKY and SHR at 6 wk. Stimulation of cAMP by salbutamol or by isoproterenol was blocked by propranolol. Neither agonist increased guanosine 3',5'-cyclic monophosphate. These data indicate that differences in cAMP metabolism are evident at the arteriolar level during the developmental stage of SHR hypertension. These differences may contribute to the morphological and physiological changes occurring at this time.
 ...
PMID:Elevated arteriolar adenosine 3',5'-cyclic monophosphate production by SHR. 618 Jun 47

Mechanisms of vascular hypertrophy induced by hypertension were studied in cultured aortic smooth muscle cells from spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and compared with those from normotensive Wistar-Kyoto (WKY) rats. Fetal calf serum-stimulated ornithine decarboxylase (ODC) activity of cultured smooth muscle cells was greater in SHR and SHRSP than in WKY. Beta- but not alpha-adrenergic agonist stimulated ODC activity acutely in cultured smooth muscle cells from WKY, and isoprenaline-induced activation was blocked by the beta-blocker, propranolol, and enhanced by the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine. These results indicate that cultured vascular smooth muscle cells from SHR and SHRSP are more prone to increase the protein synthesis than those from WKY through the trophic induction of ODC activity and that the regulation of ODC activity by catecholamines is mediated through beta-agonistic effect in cultured smooth muscle cells.
Hypertension
PMID:Studies of hypertension-induced vascular hypertrophy in cultured smooth muscle cells from spontaneously hypertensive rats. 619 73

1. This noradrenaline-induced accumulation of cyclic AMP is decreased in both the anterior and the posterior hypothalamus of hypertension-prone as compared with resistant rats, but is similar in the cortex. 2. The noradrenaline-induced accumulation of cyclic AMP is decreased in the posterior hypothalamus as compared with the anterior hypothalamus of both strains. 3. The decreased sensitivity to phosphodiesterase inhibitor in the hypothalamus of hypertension-prone as compared with resistant rats suggests that strain differences in phosphodiesterase activity may exist. 4. Since differences in cyclic AMP were found in the hypothalamus and the medulla oblongata, regions involved in blood pressure control, but not in the cortex, they may be relevant to the diverse susceptibility to hypertension of hypertension-prone and resistant rats.
 ...
PMID:Cyclic AMP generation in hypothalamus of hypertension-prone and -resistant rats. 625 16

Spontaneously hypertensive rats (SHRSP and SHR) and normotensive WKR were treated with hypotensive drugs, and arterial and venous enzyme activities were compared between treated and nontreated hypertensive groups. With the 4 month experiment, cholesterol esterase activity in the aorta from hypertensive SHRSP and SHR was significantly lower than that in the respective treated groups, whereas venous activity did not differ. By contrast, aortic NAGA activity was significantly higher in the hypertensive groups without any changes in venous activity. Acid phosphatase activity was unaltered. No effects of treatment were observed in the normotensive WKR. Accompanying a decrease in aortic cholesterol esterase, there was a marked increase in aortic cholesteryl esters accompanying hypertension. Aortic phosphodiesterase activity was significantly elevated in the hypertensive SHRSP and SHR compared with the respective treated groups. These results suggest that hypertension of long duration specifically decreased aortic cholesterol esterase activity with a consequent accumulation of cholesteryl esters in the aorta, and that this hemodynamic effect seemed to be partly mediated by cyclic AMP with an effect on the lysosomal membrane. These results could provide the biochemical bases for the relationship between hypertension and atherosclerosis.
 ...
PMID:Hemodynamic effects on aortic enzyme activities in spontaneously hypertensive rats. 625 51


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