Deoxycorticosterone acetate

Galisteo M, Garcia-Saura MF, Jimenez R, Villar IC, Zarzuelo A, Vargas F, Duarte J. 2004. Effects of chronic quercetin treatment on antioxidant defence system and oxidative status of deoxycorticosterone acetate-salt-hypertensive rats. Mol Cell Biochem 259 91-99. 

In contrast to patients with secondary aldosteronism (see below), these patients have low (suppressed) levels of plasma renin activity and angiotensin II. When treated with deoxycorticosterone acetate (20 mg/d intramuscularly for 3 days—no longer available in the USA) or fludrocortisone (0.2 mg twice daily orally for 3 days), they fail to retain sodium and their secretion of aldosterone is not significantly reduced. When the disorder is mild, it may escape detection when serum potassium levels are used for screening. However, it may be detected by an increased ratio of plasma aldosterone to renin. Patients are generally improved when treated with spironolactone, and the response to this agent is of diagnostic and therapeutic value. 

An overexpression of Gia-2 and Gia-3 proteins as well as their genes was shown in hearts and aorta from spontaneously hypertensive rats (SHRs), deoxycorticosterone acetate (DOCA)-salt hypertensive rats (HR), Atu-nitro-L-arginine methylester (L-NAME) HR, and 1 kidney 1 clip (1K1C) HR (Anand-Srivastava et al. 1991, 1993 Bohm et al. 1992, 1993 Thibault and Anand-Srivastava 1992 Anand-Srivastava 1993 DiFusco and Anand-Srivastava 1997, 2000 Ge et al. 1999, 2006), whereas Gsa protein and its gene were not altered in SHRs, 1K1C and L-NAME HR, and were decreased in DOCA-salt HRs (Anand-Srivastava et al. 1991 Anand-Srivastava 1992, 1993 Thibault and Anand-Srivastava 1992 DiFusco and Anand-Srivastava 1997, 2000 Ge et al. 1999, 2006). In addition, the levels of Goa in heart were not altered (Anand-Srivastava 1992). Alterations in Gi-protein levels have been shown to be reflected in altered responsiveness of adenylyl cyclase to stimulatory and inhibitory hormones in SHRs, and experimental models of hypertensive rats (Anand-Srivastava et al. 1991 Anand-Srivastava 1992). However,... 

Trimder D, Philipps RA, Risvani J, Stephenson JM Johnston CL 1992. Regulation of vasopressin receptor in deoxycorticosterone acetate salt hypertension. Hypertension 20 569-574. 

Cholestenone (derived from unreacted cholesterol) and progesterone were separated from deoxycorticosterone acetate (internal standard) by normal phase chromatography on a TSK-gel silica 150 column (4 mm x 250 mm)... 

Figure 9.85 Normal phase HPLC profiles of the reaction product of the cholesterol side chain cleavage system. Peaks were identified on the basis of their retention times. (i4) Without cholesterol oxidase treatment. Cholesterol (100 nmol) was incubated with cytochrome P450scc (70 pmol) in the presence of adrenodoxin, adrenodoxin reductase, and an NADPH-generating system. Monitoring was at 214 nm. Peaks 1, cholesterol 2, pregnenolone 3, deoxycorticosterone acetate (internal standard) (B) The reaction mixture of (A) was further incubated with cholesterol oxidase at 37°C for 10 minutes. Monitoring was at 240 nm. Peaks 1, cholestenone 2, progesterone 3, deoxycorticosterone acetate (internal standard). (From Sugano et al., 1989.)...

A number of studies suggest that supplements of vitamin Bg may have a hypotensive action. Supplements of300 mg of vitamin Bg per kg of body weight per day attenuated the hypertensive response of rats treated with deoxycorticosterone acetate (Fregly and Cade, 1995). At a more realistic level of supplementation (five times the usual amount provided in the diet), vitamin Bg prevented the development of hypertension in the Zucker fa/fa) obese rat. Withdrawal of the vitamin supplement led to the development of hypertension (Lai et al., 1996). 

FreglyMJ and Cade JR (1995) Effect ofpyridoxine and tryptophan, alone and combined, on the development of deoxycorticosterone acetate-induced hypertension in rats. Pharmacology 50, 298-306. 

Sesamin, the most abundant lignan present in sesame seed and sesame oil, was demonstrated to suppress the development of hypertension in rats induced by deoxycorticosterone acetate (DOCA) and salt (127). Dietary sesamin was also reported to effectively prevent the elevation of blood pressure and cardiac hypertrophy in two-kidney, one-clip (2k, Ic) renal hypertensive rats (128). In the stroke-prone spontaneously hypertensive rats (SHRSP), sesamin feeding was much more effective as an anti-hypertensive regimen in salt-loaded SHRSP (with 1% salt in drinking water) than in unloaded SHRSP (129). 

Spontaneously hypertensive rats can be used to screen compounds for antihypertensive effects and for effects on heart rate. The animals are dosed for one or a few days. Blood pressure and heart rate are measured by means of an inflatable cuff around the tail. Most classes of antihypertensives will be detected. Agents such as beta-adrenergic antagonists will be detected by decreased heart rate. Other rat models include deoxycorticosterone acetate (DOCA)-induced hypertensive, renal hypertensive (one or both renal arteries clamped), and stroke-prone spontaneously hypertensive rats. Hypertensive dogs produced by clamping one or both renal arteries may also be used to test or verify antihypertensive activity in a second species. 

Pyrazines. N-Amidino-3-amino-6-chloropyrazinecarboxamide (Xl) previously was shown to reverse the electroi e excretion effects of deoxycorticosterone acetate in the adrenalectomized rat and was shown to be a potassium-sparing natriuretic agent in the intact rat and dog. ... 

Compounds 39, 78, and 79 showed a hypotensive effect in spontaneously hypertensive rat (SHR) [80,107,108], Compound 43 showed an antihypertensive effect in deoxycorticosterone acetate (DOCA)-salt hypertensive rat. In this model, a diet containing 43 markedly suppressed the increase of blood pressure [109]. Compound 43 showed a weak inhibitory activity on angiotensin converting enzyme (ACE) [110]. Graminone B (151) inhibited the contractile response of rabbit isolated aorta [111]. 

Y Matsumura, S Kita, S Morimoto, K Akimoto, M Euruya, N Oka, T Tanaka. Antihypertensive effect of sesamine. 1. Protection against deoxycorticosterone acetate-salt-induced hypertension and cardiovascular hypertrophy. Biol Pharm Bull 18 1016-1019, 1995. 

Fregly, M. J., Effects of tryptophan on the development of deoxycorticosterone acetate (DOCA)-induced hypertension in rats, Adv. Exp. Med. Biol., 294, 619,1991. 

Dawson, R., Jr., Nagamhama, S., and Oparil, S., Central serotonergic alterations in deoxycorticosterone acetate/NaCl(DOCA/NaCl)-induced hypertension, Neuropharmacology, 27, 417, 1988. 

Fregly, M. J., Lockley, O. E., Torres, J. L., and Cade, J. R., Effect of chronic dietary treatment with nicotinic acid on the development and maintenance of deoxycorticosterone-acetate-salt-induced hypertension, Pharmacology, 37, 50, 1988. 

In approximately one-third of patients with a 21-hydroxylase defect, there is an excessive excretion of sodium chloride with abnormally high serum potassium and low serum sodium concentrations. After treatment with cortisol and deoxycorticosterone acetate (or equivalent therapeutic... 

A defect in the synthesis of aldosterone in infancy may not be permanent. Royer et al. (R18) reported two siblings with a salt-losing syndrome who responded well to 11-deoxycorticosterone acetate when one of the children was reinvestigated after 5 years, it was found that the aldosterone secretion rate was normal. Two infants studied by Russell and co-worker (R19) had salt loss in infancy and were treated with salt and 11-deoxycorticosterone acetate, but it was possible to discontinue the treatment of one infant at the age of 12 months and the other after SY2 years. 

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