Disease relevance of Apresoline

• This activity was absent in patients not treated with procainamide and in patients with lupus induced by hydralazine or quinidine [1].
• Tolerance ot hydralazine in congestive heart failure [2].
• Hydralazine-induced neonatal thrombocytopenia [3].
• It causes less tachycardia than hydralazine but may produce orthostatic hypotension, particularly after the initial dose [4].
• Results obtained with three murine tumor models clearly demonstrate that hydralazine potentiates the tumor cytotoxicity of such agents to a greater extent than it does their systemic toxicity [5].

Psychiatry related information on Apresoline

• The co-administration of the peripherally-acting, anti-hypertensive agent hydralazine did not reverse the DMI-induced REM sleep suppression [6].
• This study investigated the effects of captopril, hydralazine and losartan on the locomotor activity, tailflick and hot plate latencies in spontaneously hypertensive rats (SHR) and their genetic controls the Wistar-Kyoto rat (WKY) [7].

High impact information on Apresoline

• To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure [8].
• Thirteen consecutive patients with primary and secondary pulmonary hypertension who had normal left ventricular function were treated with hydralazine in an effort to reduce pulmonary vascular resistance and clinical symptoms [9].
• Hydralazine and the treatment of primary pulmonary hypertension [10].
• Responsiveness to hydralazine could not be restored by doubling the oral dose or by intravenous administration; tolerance was associated with fluid retention in five patients but was not reversed by intensive diuresis [11].
• Hydralazine also caused total pulmonary resistance during exercise to fall from 15.7 to 10.2 U, and cardiac output to rise from 4.7 to 7.0 liters per minute [12].

Chemical compound and disease context of Apresoline

• Susceptibility to hydralazine-induced lupus, as in idiopathic systemic lupus erythematosus, may depend partly upon genetically determined C4 levels [13].
• In addition, while all 5 patients experienced chest pain in response to bethanechol alone, only 1 of 5 experienced chest pain in response to bethanechol after previous hydralazine administration; 3 patients had chest pain after previous administration of isosorbide [14].
• PATIENTS: Fifteen patients referred for management of refractory hypertension and found to have a seated diastolic blood pressure greater than 95 mm Hg while taking a standard dose of hydrochlorothiazide, propranolol, and hydralazine or its equivalent for at least 4 weeks [15].
• Prazosin and hydralazine in congestive heart failure. Regional hemodynamic effects in relation to dose [16].
• Hemodynamic effects of nitroprusside and hydralazine in experimental cardiac tamponade [17].

Biological context of Apresoline

• Despite marked decreases in systemic vascular resistance (40 per cent; P less than 0.001), hydralazine produced only moderate decreases in pulmonary arteriolar resistance (21 per cent), without improving stroke volume or pulmonary-artery pressure [9].
• The beneficial effect of PDE inhibitors was not due to a moderate decrease (approximately -20%) in systolic blood pressure (SBP); as a similar decrease in SBP due to administration of hydralazine, a drug devoid of PDE inhibitory effect, did not reduce severity of MSGN in ATS-injected rats [18].
• Effects of hydralazine-induced vasodilation on the energy metabolism of murine tumors studied by in vivo 31P-nuclear magnetic resonance spectroscopy [19].
• The effects of hydralazine on tumor energy metabolism and on some cardiovascular parameters were measured [19].
• Human antigen-specific CD4+ T cells become autoreactive after treatment with various DNA methylation inhibitors, including 5-azacytidine, procainamide, and hydralazine [20].

Anatomical context of Apresoline

• Rest and exercise hemodynamic effects of oral hydralazine in patients with coronary artery disease and left ventricular dysfunction [21].
• Hydralazine produced vasodilation in the coronary, skeletal muscle (quadriceps), splanchnic, and renal circulations in normal dogs [22].
• Hepatocytes from rapid and slow acetylator rabbits maintained in culture the difference in acetylation rates that existed in vivo, DNA repair, an index of DNA damage, was produced by hydralazine in hepatocytes from slow acetylator rabbits but not in those from rapid acetylators [23].
• Monocytoid cell binding to aortic endothelium was also significantly increased in L-NA (P < .05); hydralazine normalized blood pressure but did not reduce monocytoid cell binding [24].
• Vasodilative effect of hydralazine in awake dogs: the roles of prostaglandins and the sympathetic nervous system [22].

Associations of Apresoline with other chemical compounds

• A similar pattern of blood pressure decrement and potentiation was seen in genetically hypertensive rats when propranolol or saralasin treatment preceded hydralazine [25].
• A solution of 0.125% 1-hydrazinophthalazine hydrochloride, an antihypertensive drug widely used in humans, was given continuously in drinking water for the life-spans of randomly bred Swiss mice [26].
• Phenylephrine decreased and hydralazine increased normal tissue perfusion as indicated by cardiac output [27].
• Use of fluorine-19 nuclear magnetic resonance spectroscopy and hydralazine for measuring dynamic changes in blood perfusion volume in tumors in mice [28].
• Hydralazine doses greater than or equal to 2.0 mg/kg given ip were associated with a decrease in PCr, nucleotide triphosphate, and pH, and an increase in Pi (P less than .01 for control vs. 10 mg hydralazine/kg) [19].

Gene context of Apresoline

• CONCLUSION: Hydralazine reproduces the lupus ERK pathway signaling abnormality and its effects on DNMT expression, and inhibiting this pathway induces autoimmunity [29].
• Murine T cells treated with hydralazine or an ERK pathway inhibitor were injected into mice and anti-DNA antibodies were measured by enzyme-linked immunosorbent assay [29].
• Furthermore, although hydralazine significantly reduced JNK activity (-56 +/- 3%), ERK1/ERK2 activities were unaffected [30].
• Hamster NAT2 has similar substrate specificity to human NAT1, acetylating para-aminobenzoate but not arylhydrazine and hydralazine compounds [31].
• It is shown that hydralazine, isoniazid and penicillamine inhibit the covalent binding of C4 to a complement-activating surface and that the drugs themselves become covalently bound to C4 [32].

Analytical, diagnostic and therapeutic context of Apresoline

• To examine the importance of left ventricular chamber size in determing the response to vasodilator therapy, we performed echocardiography in 40 patients with chronic refractory heart failure before they were treated with oral hydralazine [33].
• Hydralazine-induced tumor hypoxia: a potential target for cancer chemotherapy [5].
• Thus, hyperimmunization of rabbits with hydralazine-protein conjugates may provide a useful animal model of SLE [34].
• Central hemodynamic variables and regional blood flow and vascular resistances were ascertained in patients with severe congestive heart failure before and after the oral administration of prazosin hydrochloride or hydralazine [16].
• Intravenous injection of hydralazine (0.3 mg/kg) reduced SVR in all but two patients [35].

References