Disease relevance of Decortin

• (f) In rats depleted of potassium by low potassium intake or by production of DOCA hypertension, an inhibition of skeletal muscle Na+, K(+)-ATPase ion pump activity is directed by hypothalamic centers and involves inhibition by alpha-adrenergic activity of slow twitch fibers and inhibition by undetermined humoral factors of fast twitch fibers [1].
• After an acid load in the absence of Na+ and HCO3-, pHi response to basolateral Na+ addition was stimulated (+66%) by acidosis, but not by DOCA [2].
• When 10-15 mg i.m. of desoxycorticosterone acetate (DOCA) was given daily, five dogs developed sodium retention and ascites, while four escaped from DOCA [3].
• A differential increase in ventricular weight to body weight (hypertrophy) occurred at 3 weeks in the SHR and aortic constriction models and at 4 weeks in the DOCA salt model [4].
• The ET(A) antagonist prevented cardiac fibrosis in DOCA-salt rats [5].

Psychiatry related information on Decortin

• Daily treatment with DOCA with no opportunity to ingest saline produced a rightward shift in the midpoint (effective current 50) of lateral hypothalamic self-stimulation (LHSS) current-response functions and reduced intakes of a palatable sucrose solution [6].
• 1. This study investigated the effects of dietary modification of prostaglandin (PG) synthesis on blood pressure regulation in DOCA/salt-treated rats [7].

High impact information on Decortin

• Treatment of mice with oral tetrahydrobiopterin reduces vascular ROS production, increases NO production as determined by electron spin resonance measurements of nitrosyl hemoglobin, and blunts the increase in blood pressure due to DOCA-salt hypertension [8].
• Endothelium-dependent vasodilation is only minimally altered in vessels of mice with DOCA-salt hypertension but seems to be mediated by hydrogen peroxide released from uncoupled eNOS, since it is inhibited by catalase [8].
• Blood pressure of DOCA-salt rats treated with MAb[KY-ANP-II] was significantly higher than that of DOCA-salt rats treated with MAb[KY-ANP-I] throughout 8 wk of DOCA and 1% saline administration [9].
• The administration of MAb[KY-ANP-II] also significantly attenuated exaggerated diuresis and natriuresis in DOCA-salt rats compared with those treated with MAb[KY-ANP-I] [9].
• In the lungs, aorta, mesenteric arteries, and adrenal medulla, ACE labeling was highest in the 2K-1C group, intermediate in the 1K-1C and control groups, and lowest in the DOCA-salt group [10].

Chemical compound and disease context of Decortin

• Partial destruction of central adrenergic neurons by intraventricularly injected 6-hydroxydopamine prevents the development of DOCA/NaCl, renal, and neurogenic hypertension and alters the pattern of blood pressure rise in spontaneously hypertensive rats [11].
• Vasopressin-central nervous system interactions in the development of DOCA hypertension [12].
• Sensitivity of caudal arteries and the mesenteric vascular bed to norepinephrine in DOCA-salt hypertension [13].
• The involvement of kinins in the antihypertensive effect of captopril in DOCA-salt hypertension supports the contention that the kallikrein-kinin system contributes to blood pressure regulation in this hypertension model [14].
• The activity of the sodium-potassium (Na+-K+) pump in arterial tissue from rats with chronic DOCA-salt or one-kidney Grollman renal hypertension was assayed in vitro as the rate of ouabain-sensitive 86Rb+ uptake [15].

Biological context of Decortin

• In all four dogs who escaped from DOCA, the PCA was widely patent and the mean pressure gradient was only 1.6 cm H2O [3].
• Isolated renal cortical collecting tubules obtained from rabbits treated chronically with desoxycorticosterone acetate (DOCA) have been found to possess elevated transepithelial potential differences and a greatly increased capacity for ion transport [16].
• However, in DOCA-salt kidneys, BQ-3020 caused renal vasoconstriction (RPP, +5.4 +/- 2.4%, P < .01 versus control) and a much smaller NO release (+1.1 +/- 0.4 fmol.min-1.g-1 kidney wt, P < .01 versus control) [17].
• Natriuresis of DOCA rats was significantly greater than that of either normal or responding NaD rats [18].
• To investigate the possible contributions of cardiac volume overload and cardiac sympathetic hyperactivity in the effects of sodium on cardiac mass, we evaluated the effects of treatment with saline (1%) and deoxycorticosterone acetate + saline (DOCA/saline) for 10 days and 3 and 6 weeks on ventricular anatomy and intracardiac pressures [19].

Anatomical context of Decortin

• Methylprednisolone and DOCA increased electrolyte and water transport and Na-K-ATPase activity concomitantly in specific segments of small intestine and colon [20].
• In the kidney, anterior pituitary, testis, and choroid plexus of the brain, ACE levels correlated negatively with PRA, with lowest ACE levels in the 2K-1C group and highest levels in the DOCA-salt group [10].
• Structural exmination of tubules from rabbits exposed to either DOCA or dexamethasone for 11--18 d reveals a marked increase in basolateral cell membrane area in these tubules [16].
• In DOCA-salt rats, interstitial and perivascular collagen density was increased in the subendocardial and midmyocardial regions of the left ventricle (3- to 4-fold, P:<0.05), whereas in subepicardial myocardium, the increase was predominantly perivascular [5].
• METHODS AND RESULTS: Rats were made hypertensive after one renal artery was clipped (two kidney, one-clip renal model) or after the administration of deoxycorticosterone and salt (DOCA-salt model) [21].

Associations of Decortin with other chemical compounds

• Cilazapril had a marked preventive effect on neointima formation in normotensive rats, spontaneously hypertensive rats, and two-kidney, one-clip rats but was ineffective in DOCA rats [22].
• To investigate possible relationships between mineralocorticoids, the renal kallikreinkinin system, and renal prostaglandins, we studied the effects of aldosterone and deoxycorticosterone acetate (DOCA) and of an inhibitor of kallikrein, aprotinin, on the urinary excretion of kallikrein and prostaglandin E-like substance (PGE) by the conscious rat [23].
• Similarly, injections of DOCA (5 mg/day) into 14 rats increased the excretion of PGE and kallikrein, measured before and after 10 days of treatment, from 41.6 +/- 3.9 ng/day and 39.4 +/-4.9 U/day to 194.3 +/- 20.7 ng/day (P less than 0.001) and 90.6 +/- 14.7 U/day (P less than 0.001), respectively [23].
• Captopril, candesartan, and spironolactone reversed the increased deposition of perivascular and interstitial collagen in DOCA-salt rats; the increased cardiac fibronectin deposition was reversed by candesartan and spironolactone [24].
• Activation of NF-kappa-B and expression of I-kappa-B-alpha in DOCA-salt rats were normalized by fenofibrate [25].

Gene context of Decortin

• Increased renal medullary endothelin-1 synthesis in prehypertensive DOCA- and salt-treated rats [26].
• In the kidneys, the density of the ETB receptor subtype was upregulated in DOCA-salt and 1K1C rats from 160 +/- 8 to 217 +/- 12 and 190 +/- 2 fmol/mg (P < 0.05), respectively, and ETA tended to be downregulated (P = 0.057) [27].
• METHODS: The expression of angiotensin II receptor subtype (AT1A and AT1B) mRNAs was studied by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in the four zones of the kidneys of Sabra rats, sensitive or resistant to DOCA salt-induced hypertension (SBH/y and SBN/y, respectively) [28].
• Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase [29].
• Specifically, in the hypothalamic paraventricular nucleus, treatment with DEX or DOCA + DEX increased AT1 binding [30].

Analytical, diagnostic and therapeutic context of Decortin

• Plasma renin activity (PRA) was highest in the 2K-1C group (6.20 +/- 2.17 ng/ml per h), intermediate in the 1K-1C group (2.19 +/- 0.62 ng/ml per h) and control group (3.20 +/- 0.53 ng/ml per h), and lowest in the DOCA-salt group (0.07 +/- 0.06 ng/ml per h) [10].
• Adrenalectomy had no influence on the tumor growth in PI-bearing animals, but DCA injections stimulated secretion production by both tumor cells and normal mammary cells [31].
• Maximum induction was 10-fold over control at 5 weeks in the aortic constriction model, 8-fold at 3 weeks in the SHR, and 6-fold at 6 weeks in the DOCA salt model [4].
• Northern blot analysis revealed that renal ETB mRNA was significantly decreased in DOCA-salt rat kidneys compared with controls (0.36 +/- 0.13 versus 1.00 +/- 0.23, P < .05) [17].
• Normal sodium intake, local denervation, and peripheral sympathectomy had no effect on the development of these vascular changes in DOCA-treated rats [32].

References