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)

The effect of glucocorticoids on the atrial natriuretic factor (ANF)-mediated formation of cyclic guanosine monophosphate (cGMP) by intact vascular smooth muscle cells (VSMC) was studied in rats. Cultured VSMC were obtained from the renal arteries of 14-week-old Wistar rats by the explant method. Micromolar concentrations of dexamethasone, given as pretreatment for 48 hours, suppressed the ANF-mediated response. The dexamethasone-induced suppression was detectable at 6 hours and reached a maximum 24 hours after administration in a dose-dependent manner. Inhibitors of protein synthesis blocked this effect of the glucocorticoid. The basal activity of guanylate cyclase in the dexamethasone-treated cells was lower than in the control cells. Other steroids having glucocorticoid action mimicked this suppression of the ANF-mediated response. This suppression was blocked by a glucocorticoid receptor antagonist. The results suggest that glucocorticoids suppress ANF-mediated cGMP formation by VSMC through glucocorticoid type II receptors and the induction of protein synthesis. Suppression of the ANF-mediated response may play a role in glucocorticoid-induced hypertension.
Hypertension 1990 Nov
PMID:Glucocorticoids and atrial natriuretic factor receptors on vascular smooth muscle. 217 62

The Purkinje fibers of the rabbit false tendons (chordae tendineae spuriae) are endocrine cells containing immunoreactive atrial natriuretic factor (ANF) and ANF messenger RNA (mRNA). These cells, as visualized by immunocryoultramicrotomy, contain immunoreactive ANF in their secretory granules and their Golgi complex and exhibit ANF mRNA, as visualized by in situ hybridization with an ANF complementary RNA probe. The content of immunoreactive ANF and ANF mRNA of the Purkinje fibers is midway between that of atrial and ventricular working cardiocytes. High-pressure liquid chromatography analysis of immunoreactive ANF using antibodies against the C-terminal and N-terminal moieties of the molecule indicates that part of immunoreactive ANF contained in Purkinje fibers is the propeptide [Asn1,Tyr126]ANF whereas part was nonspecifically cleaved into C-terminal and N-terminal ANF. The chordae tendineae spuriae exhibit binding sites for ANF (Kd:approximately 1.0 nM; Bmax:approximately 2.3 fmol/mg). ANF profoundly decreases basal and stimulated (epinephrine, dopamine, isoproterenol, and forskolin) adenylate cyclase activity and cyclic adenosine monophosphate (AMP) levels. ANF has little effect on norepinephrine-stimulated adenylate cyclase activity or on norepinephrine-stimulated cyclic AMP levels. ANF produces only a slight increase in guanylate cyclase activity and cyclic guanosine monophosphate levels at high (10(7)-10(6) M) concentrations. These results suggest an autocrine function for ANF in the modulation of the impulse in the peripheral conduction cells (Purkinje fibers) of the rabbit through changes in second messenger levels.
Hypertension 1989 Jun
PMID:Atrial natriuretic factor in Purkinje fibers of rabbit heart. 247 58

To ascertain whether small shifts in plasma atrial natriuretic factor (ANF) exerted biological effects in hypertension, we studied the renal, hemodynamic, and hormonal effects of ANF [human ANF-(99-126)] infused at a dose (0.75 pmol/kg/min for 3 hours) that would induce changes in plasma ANF confined to the normal, resting range, in a group of six young men with uncomplicated, mild essential hypertension. During ANF infusions, the patients excreted 11.8 +/- 2.0 mmol (mean +/- SEM) sodium more than during the time-matched placebo phase natriuresis (p less than 0.001, mean increase of 53% above placebo values). Urinary excretion of cyclic guanosine monophosphate rose to more than double (212%, p less than 0.001) placebo values. Plasma renin activity (0.4 +/- 0.05 vs. 0.9 +/- 0.12 nmol/l/hr, p less than 0.0001) and aldosterone concentrations (102 +/- 4 vs. 184 +/- 47 pmol/l, p less than 0.05) were clearly suppressed during administration of ANF. Plasma norepinephrine also fell significantly below placebo values (268 +/- 17 vs. 439 +/- 35 pg/ml, p less than 0.05). Urine volume, the excretion of electrolytes other than sodium, hematocrit, effective renal plasma flow, glomerular filtration rate, and filtration fraction were unaffected by ANF. Similarly, plasma concentrations of epinephrine, arginine vasopressin, adrenocorticotropic hormone, and cortisol were unchanged. Blood pressure and heart rate were unchanged. Minor perturbations in plasma ANF concentrations exert clear biological effects in patients with mild essential hypertension. These data suggest that such minor shifts in plasma ANF are of physiological relevance in mild hypertension and probably contribute to volume homeostasis in this condition.
Hypertension 1989 Sep
PMID:Atrial natriuretic factor in hypertension: bioactivity at normal plasma levels. 252 19

There are differences in the renal handling of sodium between spontaneously hypertensive rats (SHR) and their normotensive controls. We investigated whether this difference may be associated with changes in plasma and tissue atrial natriuretic factor (ANF) levels and with alterations in glomerular ANF receptors at 4, 8, 12, and 16 weeks of age. Age-matched Wistar-Kyoto (WKY) and Wistar rats were used as normotensive controls. Systolic blood pressure was higher in SHR at 8, 12, and 16 weeks, and cardiac hypertrophy was also present in these animals at 4 weeks. Plasma ANF C- and N-terminal concentrations were greater than in both normotensive groups at 8 and 16 weeks. ANF in the right atrium was higher in SHR than in WKY rats and identical to that in the Wistar group at 4 and 8 weeks. ANF in the left atrium was lower in SHR than in both control groups at week 12. No differences were found in ventricular ANF content. The density of glomerular ANF binding sites increased with age in WKY and Wistar rats but not in SHR. At weeks 8, 12, and 16, both normotensive groups had a higher density of binding sites than SHR, but binding site affinity was greater in SHR at weeks 8 and 12. After incubation with increasing concentrations of ANF, the production of cyclic guanosine monophosphate (cGMP) by isolated glomeruli from 16-week-old rats was lower in SHR than in both normotensive groups. We conclude that the development of hypertension in SHR is associated with higher plasma ANF levels and decreased glomerular ANF receptor density and glomerular cGMP production.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1989 Jun
PMID:Glomerular atrial natriuretic factor receptors in spontaneously hypertensive rats. 254 18

Endothelium-dependent vasodilators, nitrates, and atrial natriuretic factor relax blood vessels by increasing vascular cyclic guanosine monophosphate (cGMP). The mechanisms by which cGMP relaxes vascular smooth muscle (VSM) are not known. Since contraction of VSM is associated with increased intracellular calcium and pH, we hypothesized that cGMP may decrease vascular tone by lowering ionized, intracellular calcium [( Ca2+]i) and pH. We used microfluorometry to measure cGMP-induced changes in intracellular calcium and pH of cultured A7r5 VSM cells after stimulation with contractile agonists. A cGMP analogue, 8-Br-cGMP, blocked vasopressin- but not thrombin-stimulated increases in [Ca2+]i. High extracellular potassium concentrations [( K+]) increased [Ca2+]i, but the attenuation of [Ca2+]i by 8-Br-cGMP was not statistically significant. 8-Br-cGMP also attenuated vasopressin- but not thrombin-stimulated alkalinization of VSM cells. cGMP may decrease vascular tone by decreasing [Ca2+]i and pH, but these changes are dependent on the contractile agonist studied.
Hypertension 1989 Jun
PMID:Effect of 8-bromo-cyclic guanosine monophosphate on intracellular pH and calcium in vascular smooth muscle. 254 26

Depressor and renal activities of atrial natriuretic factor-(99-126) were determined in conscious, unrestrained spontaneously hypertensive rats treated with a neutral endopeptidase inhibitor, SQ 29,072 (7-[[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]amino]heptanoic acid). SQ 29,072 (100 mumol/kg i.v.) prolonged the transient depressor effects of the peptide for as long as 2 hours. During the first hour after 3, 10, and 30 nmol/kg atrial natriuretic factor, urinary excretion of cyclic 3'5' guanosine monophosphate was significantly increased by 9.2 +/- 3.4, 13.0 +/- 2.2, and 12.7 +/- 4.2 nmol/kg/hr, respectively, in vehicle-treated rats and by 26.9 +/- 7.9, 52.1 +/- 11.1, and 46.4 +/- 12.2 nmol/kg/hr, respectively, in rats given 100 mumol/kg SQ 29,072. During the first hour after 3 and 10 nmol/kg atrial natriuretic factor-(99-126), the sodium loss was 161 +/- 56 and 139 +/- 42 mueq/kg/hr in vehicle-treated rats and was significantly greater (694 +/- 316 and 1,038 +/- 135 mueq/kg/hr) in rats given 100 mumol/kg SQ 29,072. After administration of 3, 10, and 30 mumol/kg SQ 29,072, the area over the curves of the depressor responses to 3 nmol/kg of the peptide increased from 297 +/- 70 to 306 +/- 108, 440 +/- 143, and 669 +/- 186 mm Hg.min, respectively, while the concurrent natriuretic responses rose from 161 +/- 56 to 250 +/- 88, 332 +/- 142, 464 +/- 164, and 694 +/- 316 mueq/kg/hr. In summary, the neutral endopeptidase inhibitor SQ 29,072 increased the magnitudes and especially the durations of the depressor, natriuretic, and cyclic guanosine monophosphate responses to exogenous atrial natriuretic factor-(99-126) in conscious spontaneously hypertensive rats, presumably by inhibition of degradation of atrial natriuretic factor in vivo. In conclusion, neutral endopeptidase inhibition offers an important new technique for enhancement and prolongation of the biological lifetime of atrial natriuretic factor.
Hypertension 1989 Jul
PMID:Potentiation of renal effects of atrial natriuretic factor-(99-126) by SQ 29,072. 254 29

Dilevalol, an agent that combines nonselective beta-blocking and beta 2-mediated vasodilating properties, was compared with placebo in 16 subjects with moderate hypertension in a double-blind crossover study. Dilevalol or a placebo was administered intravenously in bolus injections of 25, 50, and 50 mg at 15-minute intervals. Fifteen minutes after a cumulative dose of 125 mg, the blood pressure was lowered by 11/9 mm Hg, compared with 2/1 mm Hg after placebo (p less than 0.01 between groups for systolic and diastolic blood pressure), an effect that persisted for at least 105 minutes. Standing systolic blood pressure was also lowered in dilevalol-treated patients without orthostatic symptoms. No significant effects on heart rate were noted. Fifteen minutes after the last dose of dilevalol, plasma norepinephrine levels increased from a baseline of 200 +/- 24 to 495 +/- 44 pg/ml (p less than 0.01), compared with a nonsignificant rise from 262 +/- 21 to 306 +/- 28 pg/ml with placebo vehicle. Dilevalol also increased alpha-human atrial natriuretic factor by 5.4 pg/ml, compared with 0.5 pg/ml after placebo (p less than 0.01 between groups). Plasma renin activity and plasma epinephrine, aldosterone, and cyclic guanosine monophosphate levels were unchanged by dilevalol. There were no significant adverse effects with dilevalol administration. Compared with placebo, dilevalol given intravenously appears to be safe and effective antihypertensive treatment.
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PMID:Comparison of intravenous dilevalol with placebo in moderate hypertension. 255 60

The natriuretic effects of atrial peptide hormones have been attributed, at least in part, to their stimulation of guanylate cyclase activity in renal cell membranes. The effects of atrial natriuretic factor (ANF) on stimulation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation were investigated in cloned human kidney tumor (hKT) cells and parent cells from a human renal tumor epithelial cell line (SK-NEP-1). Human ANF-(99-126) (10(-6)M) stimulated (p less than 0.001) cellular cGMP accumulation in a dose-dependent manner from a basal level of 0.26 +/- 0.04 to 3.73 +/- 0.81 pmol/mg protein/5 mi (mean +/- SEM, n = 13). ANF stimulation of cGMP accumulation was specific, in that high concentrations (10(-6)M) of atriopeptin I [rat ANF-(103-123)], angiotensin II, arginine vasopressin, and amiloride (10(-4)M) did not increase basal cGMP. Amiloride (10(-4)M) enhanced (p less than 0.01, n = 6) the ANF stimulation of cGMP accumulation (1.24 +/- 0.39 pmol/mg protein/5 min), particularly at low doses of ANF (10(-10)M) where stimulation by ANF without amiloride (0.34 +/- 0.08 pmol/mg protein/5 min) was barely distinguishable from a basal level (0.19 +/- 0.02 pmol/mg protein/5 min) of cGMP accumulation. The stimulatory effect of ANF (1.59 +/- 0.07 pmol/mg protein/5 min) was attenuated (0.75 +/- 0.06 pmol/mg protein/5 min, p less than 0.01, n = 6) by preincubation of the cells with pertussis toxin but not by cholera toxin. ANF (4.56 +/- 0.93 pmol/mg protein/5 min, n = 8) did not affect cAMP accumulation (4.32 +/- 0.98 pmol/mg protein/5 min) in hKT cells. This is the first report of an ANF responsive human renal cell line, and its use should facilitate investigation of ANF-receptor interactions.
Hypertension 1989 Jun
PMID:Atrial natriuretic factor effects on cyclic nucleotides in a human renal cell line. 256 5

We investigated the role of endothelium derived relaxing factor (EDRF) and cyclic guanosine monophosphate (cGMP) in the altered vascular reactivity of hyperthyroidism (HT). Rats were given daily injections of triiodothyronine (T3), 50 micrograms/100 g body weight for two weeks, and they had significantly higher serum levels of T3 compared to untreated, control rats (493 +/- 82 vs. 58 +/- 7 ng/dl, p less than 0.05) and significant elevations in their systolic blood pressure (188 +/- 6 vs 126 +/- 3 mm Hg, p less than 0.05). Vascular reactivity was studied in isolated muscle baths; cGMP was measured by RIA. There were no differences in contractile responses to phenylephrine (PE) in isolated aortae from the HT and control rats, but aortae from the HT rats contracted with PE relaxed less to acetylcholine (Ach); the calcium ionophore, A23187; and sodium nitroprusside (SNP). Sensitivity to atrial natriuretic factor (ANF) and 8-Br cGMP was unaltered. Blood vessels from HT rats generated significantly less cGMP in response to Ach, SNP, and ANF. Treatment of the hypertension in the HT rats which hydralazine or propranolol restored the vascular relaxation response to Ach but not SNP; cGMP responses remained blunted. These data suggest that endothelium dependent vasodilators may induce relaxation independent of elevations of cGMP in aortae from HT rats.
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PMID:The endothelium and cyclic guanosine monophosphate in hyperthyroid-induced hypertension. 282 95

Both our previous and the present studies established that increases in cyclic guanosine monophosphate (cGMP) reflect the activity of atrial natriuretic factor (ANF). The ANF message is transmitted by particulate guanylate cyclase, which appears to be in intimate contact with the ANF receptor since stimulation of particulate guanylate cyclase is observed even after dispersion of the membranes. The stimulation of smooth muscle and endothelial cells in culture leads to egression of cGMP to extracellular medium where it accumulates for over 2 h. The signal of the extracellular cGMP is magnified and prolonged compared to the intracellular signal. The stimulation of cGMP production by ANF in vascular smooth muscle and endothelial cells appears to be relatively irreversible and the responsiveness is down-regulated by prior exposure to low doses of ANF. Cyclic guanosine monophosphate can also serve as a marker for ANF action. Atrial natriuretic factor fragments of different potencies exert a biological activity that correlates with ANF-induced cGMP increases. In hypertensive rats and monkeys, where acute infusion of ANF leads to an exaggerated diuresis and natriuresis, urinary cGMP does not appear to be different. Overall, cGMP appears to be a mediator and a marker of ANF biological activity and may serve as a useful tool in the study of pathogenesis of hypertension.
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PMID:Cyclic GMP as mediator and biological marker of atrial natriuretic factor. 287 13


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