BACKGROUND Organic nitrates such as nitroglycerin and isosorbide dinitrate are useful in the treatment of congestive heart failure (CHF), but tolerance develops rapidly during continuous administration. Because combination therapy of nitrate and hydralazine has been shown to provide both short- and long-term benefit but nitrate alone produces hemodynamic tolerance, we questioned whether hydrala...

Changes in circulating catecholamines and transmyocardial catecholamine balance associated with improved left ventricular function were studied in patients with chronic heart failure after treatment with captopril (10 patients) and hydralazine in combination with isosorbide dinitrate (eight patients). Cardiac performance improved in response to both captopril and hydralazine-nitrate treatment. ...

Hydralazine is an antihypertensive drug that elicits andti-nuclear antibodies in patients as an adverse effect. We investigated the ability of hydralazine to promote/stabilize the triplex DNA form of poly(dA).2poly(dT). Under conditions of low ionic strength, the polynucleotide melted as a double helix with a melting temperature (Tm) of 55.3 degrees C. Hydralazine destabilized this duplex form ...

It has been reported that nitroglycerin (GTN) tolerance can be prevented by the concurrent administration of hydralazine. Although the mechanism of this effect remains unknown, it is possible that hydralazine modifies counter-regulatory responses to nitrate administration. To address this question, we examined the impact of hydralazine therapy on the development of tolerance during sustained th...

The purpose of this study was to examine effects of antihypertensive treatment on structure and mechanics of cerebral arterioles and the incidence of stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Treatment of hypertension was begun at 3 months of age with cilazapril (45 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, or with hydralazine (18 mg/kg/day). Cilazapril...

The vasodilator hydralazine, used clinically in cardiovascular therapy, relaxes arterial smooth muscle by inhibiting accumulation of intracellular free Ca via an unidentified primary target. Collagen prolyl hydroxylase is a known target of hydralazine. We therefore investigated whether inhibition of other members of this enzyme family, namely the hypoxia-inducible factor (HIF)-regulating O2-dep...

Acrolein is a highly reactive alpha,beta-unsaturated aldehyde that readily alkylates nucleophilic centers in cell macromolecules. Typically, such reactions proceed via Michael addition chemistry, forming adducts that retain an electrophilic carbonyl group. Since these species participate in secondary deleterious reactions, we hypothesize that inactivation of carbonyl adducts may attenuate acrol...

Hydralazine has been shown to reduce mortality in patients with congestive heart failure when given concomitantly with isosorbide dinitrate. Recently, we demonstrated that nitrate tolerance is in part due to enhanced vascular superoxide .O2- production. We sought to determine mechanisms whereby hydralazine may prevent tolerance. Rabbits either received no treatment, nitroglycerin patches (1.5 m...

The vasodilator hydralazine, used clinically in cardiovascular therapy, relaxes arterial smooth muscle by inhibiting accumulation of intracellular free Ca2+ via an unidentified primary target. Collagen prolyl hydroxylase is a known target of hydralazine. We therefore investigated whether inhibition of other members of this enzyme family, namely the hypoxia-inducible factor (HIF)-regulating O2-d...