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

Changes in cyclic nucleotide metabolism similar to those characteristic of the chronic forms of hypertension were observed in an acute neurogenic form of hypertension in rats produced by electrolytic lesions of the nucleus tractus solitarii. These changes that were evident 2 hr after the lesions were made included decreased cyclic AMP levels in the heart, increased cGMP:cAMP ratio, cAMP phosphodiesterase (3':5'-cAMP 5'-nucleotidohydrolase, EC 3.1.4.17) and guanylyl cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2) activities in the aorta and decreased snesitivity of adenylyl cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) in both the aorta and heart to stimulation by the beta-adrenergic stimulant isoproterenol. These changes appear to depend on catecholamine release and are not due to mechanical distortion secondary to the increased arterial pressure. These studies provide biochemical support to the concept that the sympathetic nervous system may play a critical role in the initiation of the hypertensive syndrome and that chronic hypertension could result from the fixation of the biochemical effects of increased sympathetic activity.
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PMID:Changes in cyclic nucleotide metabolism in aorta and heart of neurogenically hypertensive rats: possible trigger mechanism of hypertension. 23 70

The aim of this study was to investigate the effects of dietary calcium and sodium on blood pressure (BP) in normotensive rats (Wistar, WKY), spontaneously hypertensive rats (SHR) and Dahl rats and on calmodulin (CaM) activator, a newly-discovered hydrophobic compound that increases CaM activity in SHR and spontaneously hypertensive mice (SHM) tissues (J Clin Invest 82:276, 1988). The CaM activator was assessed by its capacity to stimulate a CaM-dependent phosphodiesterase (CaM-PDE). In Wistar rats, which were fed a high sodium diet (3.5%), BP significantly increased (P less than .01) from 106 +/- 4 to 128 +/- 8 mm Hg in parallel to an elevation of the CaM activator from 1.57 +/- 0.14 to 2.80 +/- 0.18 U. WKY, SHR, and Dahl salt-sensitive (DS/JR) and salt-resistant (DR/JR) rats were given low (0.15%) or high (2.5%) Ca diets, both with 1% sodium. In rats receiving high dietary Ca the progression of hypertension diminished and BP was lower in SHR (156 +/- 4 mm Hg) and young DS/JR rats (125 +/- 3 mm Hg) than in those receiving low dietary Ca (192 +/- 10 and 183 +/- 2 mm Hg). There was a concomitant decrease of CaM activator in these animals to levels indistinguishable from those of WKY or DR/JR rats. The activator was also found in the heart, kidneys and erythrocytes from SHM. In the presence of exogenously added CaM, lipidic extracts from the SHM heart showed augmented CaM-PDE activity relative to normotensive preparations. This difference was eliminated by trifluoperazine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increase of calmodulin activator in hypertension. Modulation by dietary sodium and calcium. 222 70

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.
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PMID:Aberrations of cyclic nucleotide metabolism in the hearts and vessels of hypertensive rats. 415 74

Pulmonary edema which develops during acute myocardial infarction is generally believed to result solely from pulmonary microvascular hypertension. However, patient with myocardial infarction and pulmonary edema occasionally are found to have normal pulmonary wedge pressure. We report data indicating that pulmonary edema develops after coronary artery ligation despite stable microvascular pressure. Four groups of open-chest dogs were studied: (1) nine dogs with left anterior descending coronary artery ligation, (2) seven dogs with sham coronary ligation, (3) seven dogs ligated after beginning an infusion of indomethacin (5 mg/kg per hr), and (4) five dogs ligated after an infusion of the drug's vehicle was begun. Extravascular lung water and pulmonary blood volume were measured at hourly intervals during the 2 hours before and after coronary ligation or sham ligation. Gravimetric lung water was measured immediately thereafter. Changes of net pulmonary intravascular driving force (the difference of microvascular hydrostatic and oncotic pressure) after ligation or sham ligation were small and comparable in all groups. Pulmonary blood volume did not change in any group. Pulmonary extravascular water volume remained constant in the sham group but rose significantly in the ligated group. Gravimetric lung water also was significantly higher in the latter group. We interpret these results to indicate that factors other than microvascular pressure can mediate the formation of these results to indicated that factors other than microvascular pressure can mediate the formation of edema during acute myocardial infarction; increased pulmonary microvascular permeability may be responsible. Indomethacin infusion blocked the formation of edema after coronary ligation, even though net microvascular driving force was highest in this group. Infusion of the vehicle alone did not prevent edema. The mechanism by which indomethacin exerts this protective effect is unclear but is probably a result of its inhibition of cyclo-oxygenase or cyclic nucleotide phosphodiesterase.
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PMID:Non-hydrostatic pulmonary edema after coronary artery ligation in dogs. Protective effect of indomethacin. 705 61

The positive inotropic agents, including beta-adrenergic receptor agonists and PDE III inhibitors, are reviewed to explain their mechanisms of action, pharmacology, and clinical usage. New cardiotonic drugs, such as dopexamine and dobutamine (beta-adrenergic receptor agonists) and amrinone, milrinone, and enoximone (PDE III inhibitors), have important roles for the treatment of perioperative acute heart failure or acute deterioration of congestive heart failure. PDE III inhibitors have important roles as effective inodilator agents, and understanding their actions, pharmacology, and appropriate usage is important. Nicardipine, the first dihydropyridine calcium-channel blocker available for intravenous use, represents an arterial-specific vasodilator that offers an important therapeutic approach to treat perioperative hypertension.
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PMID:New cardiac drugs. 763 56

1. Thyroid hormone (L-thyroxine, 10(-10) mol/l) incubated in vitro with human erythrocyte membranes induced the release of a soluble calmodulin-like material, the 3':5'-cyclic nucleotide phosphodiesterase-stimulating activity of which was at least six-fold greater than its concentration measured by a specific calmodulin radioimmunoassay. 2. The material had the characteristics of calmodulin in that it stimulated both phosphodiesterase and erythrocyte Ca(2+)-ATPase activities, cross-reacted with and was neutralized by anti-calmodulin antibody, was adsorbed by phenothiazine-Sepharose and was heat-stable. Control supernatant from the incubation of membranes in the absence of thyroxine contained calmodulin, the bioactivity of which was not enhanced beyond that predicted from radioimmunoassay. Subsequent addition of thyroxine did not increase calmodulin bioactivity. Calmodulin-agarose removed calmodulin-enhancing activity from the supernatant. 3. Thus, the enhancing factor(s) appears to interact directly with calmodulin. These observations indicate that thyroid hormone promotes the release from human erythrocyte membranes of a soluble factor (or factors) which binds to calmodulin and significantly increases its bioactivity. This enhancing activity is similar to that of a calmodulin activator described in a rat model of hypertension (S.-L. Huang et al., J Clin Invest 1988; 82: 276-81).
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PMID:Thyroid hormone stimulates release of calmodulin-enhancing activity from human erythrocyte membranes in vitro. 838 86

In the isolated, perfused rat thick ascending limb (THAL), L-arginine (L-Arg) stimulates endogenous nitric oxide (NO) production, which inhibits NaCl absorption. However, the intracellular cascade responsible for the effects of NO has not been studied. We hypothesized that endogenous NO inhibits THAL NaCl transport by increasing cGMP, which activates protein kinase G (PKG) and cGMP-stimulated phosphodiesterase (PDE II), which, in turn, decreases cAMP levels. THALs from rats were isolated and perfused, and net chloride flux (J(Cl-)) was measured. L-Arg was used to stimulate NO production. Adding L-Arg (0.5 mmol/L) to the bath decreased J(Cl-) from 154.4+/-9.9 to 101.9+/-14.1 pmol. mm(-1). min(-1), a 35.2% decrease (n=6; P<0.05). In the presence of the soluble guanylate cyclase inhibitor LY-83583 (10 micromol/L), adding L-Arg to the bath did not affect THAL J(Cl-) (143.7+/-28.1 versus 136.7+/-22.2 pmol. mm(-1). min(-1); n=6). LY-83583 alone had no effect on J(Cl-). In the presence of the PDE II inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) 50 micromol/L, L-Arg reduced J(Cl-) by only 13% (142.1+/-8.9 versus 122.7+/-11.5 pmol. mm(-1). min(-1); P<0.05; n=6). EHNA alone had no effect on THAL J(Cl-). In the presence of 10(-5) mol/L dibutyryl (db)-cAMP, L-Arg did not significantly reduce J(Cl-) (116.3+/-18.2 versus 102.6+/-15.6 pmol. mm(-1). min(-1); n=6). db-cAMP (10(-5) mol/L) had no effect on THAL J(Cl-). In the presence of the PKG inhibitor KT-5823 (2 micromol/L), L-Arg lowered J(Cl-) from 142.6+/-14.1 to 85.9+/-8.3 pmol. mm(-1). min(-1), a decrease of 35.6% (n=8; P<0.05). We conclude that (1) endogenous NO inhibits THAL J(Cl-) by stimulating soluble guanylate cyclase and increasing cGMP; (2) NO inhibits THAL J(Cl-) by stimulation of PDE II, which, in turn, decreases cAMP levels; and (3) PKG does not mediate NO-induced inhibition of THAL J(Cl-).
Hypertension 2001 Feb
PMID:NO Inhibits NaCl absorption by rat thick ascending limb through activation of cGMP-stimulated phosphodiesterase. 1123 Mar 20

We investigated the mechanisms of action of S-petasin and S-isopetasin, from Petasites formosanus Kitamura which is used as a folk medicine for treating hypertension, tumors, and asthma in Taiwan. The tension changes of tracheal segments were isometrically recorded on a polygraph. S-Petasin and S-isopetasin non-competitively inhibited cumulative histamine-, and carbachol-induced contractions with an exception that S-isopetasin produced a parallel, rightward shift of the concentration-response curve of carbachol in a competitive manner. S-Petasin also non-competitively inhibited cumulative Ca(2+)-induced contractions in depolarized (K+, 60 mM; histamine, 100 microM; or carbachol, 10 microM) guinea-pig tracheas. S-Isopetasin did in depolarized (K+, 60 mM) trachea too. The nifedipine (10 microM)-remaining tension of carbachol (0.2 microM)-induced precontraction was further relaxed by S-petasin or S-isopetasin, suggesting that no matter whether either blocked VDCCs or not, S-petasin or S-isopetasin may have other mechanisms of relaxant action. The relaxant effect of S-petasin or S-isopetasin was unaffected by the presence of propranolol (1 microM), 2',5'-dideoxyadenosine (10 microM), methylene blue (25 microM), glibenclamide (10 microM), N omega-nitro-L-arginine (20 microM), or alpha-chymotrypsin (1 U/ml). However, S-petasin (100-300 microM), but not S-isopetasin, significantly inhibited cAMP-, but not cGMP-dependent PDE activity of the trachealis. The above results reveal that the mechanisms of relaxant action of S-petasin and S-isopetasin may be primarily due to its non-specific antispasmodic and antimuscarinic effects, respectively.
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PMID:Mechanisms of relaxant action of S-petasin and S-isopetasin, sesquiterpenes of Petasites formosanus, in isolated guinea pig trachea. 1134 92

The objective of this study was to test the hypothesis that renal interstitial (RI) cGMP is natriuretic in vivo. In conscious rats (n=8), urinary sodium excretion (U(Na)V) was significantly greater on days 3 and 4 of RI infusion of cGMP (1.17+/-0.14 and 1.61+/-0.11 mmol/24 h, respectively) than during vehicle infusion (0.56+/-0.15 and 0.70+/-0.17 mmol/24 h, respectively) (P<0.01). Similarly, U(Na)V was greater on days 3 and 4 of RI infusion of 8-bromo-cGMP (2.15+/-0.42 and 2.16+/-0.1 mmol/24 h, respectively). Protein kinase G inhibitor Rp-8-pCPT-cGMPS reduced cGMP-induced and 8-bromo-cGMP-induced U(Na)V to control levels. Acute RI infusion of L-arginine (L-Arg, 40 mg. kg(-1). min(-1)), but not D-arginine, caused an increase in U(Na)V from 1.65+/-0.11 to 4.07+/-0.1 micromol/30 min (P<0.01). This increase was blocked by RI infusion of N(G)-nitro-L-arginine methyl ester (100 ng. kg(-1). min(-1)) by the phosphodiesterase (PDE II) activator 5,6DMcBIMP (0.01 micromol/microL), by PDE II (0.03 U. kg(-1). min(-1)) itself, or by the soluble guanylyl cyclase inhibitor 1-H-[1,2,4]oxadiazolo-[4,2-alpha]quinoxalin-1-one (ODQ, 0.12 mg. kg(-1). min(-1)). The PDE II activator also blocked L-Arg-stimulated cGMP levels. The NO donor S-nitroso-N-acetylpenicillamine (SNAP, 0.12 micromol. L(-1). kg(-1). min(-1)) increased U(Na)V from 1.65+/-0.11 to 2.93+/-0.08 micromol/30 min (P<0.01), and this response was blocked completely by ODQ. Renal arterial but not RI administration of the heat-stable enterotoxin of Escherichia coli induced natriuresis. RA infusion of cGMP (3 microg/min) increased U(Na)V, renal blood flow (RBF), and glomerular filtration rate (GFR). Renal cortical interstitial cGMP infusion increased U(Na)V with no effect on total RBF, renal cortical blood flow, or GFR. Similarly, the natriuretic actions of renal interstitial L-Arg or SNAP were not accompanied by any change in RBF or GFR. Medullary cGMP infusion had no effect on U(Na)V, total RBF, or medullary blood flow. Texas red-labeled cGMP infused via the RI space was distributed exclusively to cortical renal tubular cells. The results demonstrate that RI cGMP inhibits renal tubular sodium absorption via protein kinase G independently of hemodynamic changes. These observations indicate that the cortical interstitial compartment provides a potentially important domain for cell-to-cell signaling within the kidney.
Hypertension 2001 Sep
PMID:Renal interstitial cGMP mediates natriuresis by direct tubule mechanism. 1156 96

31P MR spectroscopy was used to measure the signal intensity ratios of high-energy metabolites for the calculation of free cytosolic magnesium concentration [fMg(2+)] and pH in the calf muscles of patients with primary juvenile hypertension and of healthy controls. Surface coil and spectroscopic imaging techniques were used. In patients with hypertension, the concentrations of [fMg(2+)] was 788 +/- 33 micromol/l and intracellular pH was 7.05 +/- 0.02; these values were not significantly different from the results obtained in healthy controls ([fMg(2+)], 776 +/- 21 micromol/l and pH, 7.06 +/- 0.01). Biochemical assays of magnesium in the serum (S-Mg) and in urine (DU-Mg) confirmed this finding. Significant differences in the relative signal intensities of high-energy phosphates between patients with primary juvenile hypertension and healthy controls were observed: a) signal intensity ratios of PCr/Pi, PCr/PbetaATP, PDE/PbetaATP were increased, and b) Pi/PDe, Pi/PATP were decreased. The results were the same irrespective of whether the surface coil method or 31P spectroscopic imaging were employed.
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PMID:Concentrations of free mg2+, pH and 31P MR metabolite ratios in calf muscles of healthy controls and patients with primary juvenile hypertension. 1210 26


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