Vasodilators pulmonary hypertension

In low doses, inhaled NO may have a beneficial therapeutic effect, since NO in the inspired air leads to pulmonary vasodilation. In persistent pulmonary hypertension of the newborn, NO inhalation has already been used with some success. NO inhalation as the treatment for acute respiratory distress syndrome, however, has been disappointing. Only transient improvements of oxygenation were detected and the outcome of placebo-controlled trials did not show any improvement... 

NO activates soluble guanylyl cyclase to elevate cGMP levels in vascular smooth muscle Vasodilator relaxes other smooth muscle inhalation of NO leads to increased blood flow to parts of the lung exposed to NO and decreased pulmonary vascular resistance Hypoxic respiratory failure and pulmonary hypertension Inhaled gas Toxicity Methemoglobinemia... 

There has been a sequential comparison of inhaled nitric oxide 40 ppm with aerosolized iloprost 14— 17 micrograms in 35 adults with primary pulmonary hypertension (125). Five of the patients had minor headache and facial flushing during inhalation of iloprost, but these symptoms were short-lived and abated a few minutes after the inhalation ended. One patient had mild jaw pain after aerosolized iloprost, but again this was shortlived. There was an unexpected increase in pulmonary artery pressure in 10 patients and vascular resistance in six patients who received nitric oxide. The authors were uncertain of the cause of this increase, as nitric oxide generally behaves as a vasodilator, but they noted that... 

Nitric oxide also produces vasodilation in vascular smooth muscle. As indicated earlier, hypertension may be perpetuated by a defect in the production of nitric oxide by the vascular endothelium. In follows that providing nitric oxide directly or administering precursors for nitric oxide production may help reduce vascular resistance and decrease arterial pressure in specific hypertensive syndromes.6 To date, inhaled nitric oxide has been used to treat acute pulmonary hypertension associated with respiratory distress syndrome in new-... 

Pulmonary hypertension. This condition involves a narrowing of the pulmonary vascular bed resulting mostly from unknown causes. The disease often is progressive, associated with right ventricular overload, and all but resistant to treatment with conventional vasodilators. The endothelin antagonist, bosentan, offers a new therapeutic approach. Administration of NO by inhalation is under clinical trial. 

The main difference between PPH and HPS is to be seen in the fact that the latter reveals an impaired gas exchange with hypoxaemia and a reduction in pulmonary vascular resistance due to vasodilation. The coexistence of these two pathological conditions vasodilation on the one hand and vasoconstriction on the other hand) has recently become documented more often. Any illnesses which lead to pulmonary hypertension must be ruled out as part of the differential diagnosis. 

Felodipine is a dihydropyridine derivative with diuretic properties (1). Its diuretic properties are not unique but are shared by other dihydropyridines. Its vasodilator-related adverse effects include flushing, headache, and tachycardia (2,3). Reduced arterial oxygen saturation has been seen in patients given intravenous felodipine for pulmonary hypertension (4,5). Along with amlodipine, but unlike other calcium channel blockers, felodipine may be safer in severe chronic heart failure accompanied by angina or hypertension. 

In another study the acute response to inhaled nitric oxide and high doses of oral nifedipine or verapamil was assessed in 33 consecutive patients with primary pulmonary hypertension (2). Ten patients responded acutely to nitric oxide, nine of whom responded acutely to calcium channel blockers, without any complications. The other 23 patients failed to respond to nitric oxide and calcium channel blockers. In these non-responders there were nine serious adverse effects with calcium channel blockers. There was no clinical or baseline hemodynamic feature that predicted the acute vasodilator response. Long-term oral treatment with calcium channel blockers was restricted to the nine acute responders, and there was a sustained clinical and hemodynamic improvement in only six patients. It was concluded that nitric oxide may be used as a screening agent for safely identifying patients with primary pulmonary hypertension who may benefit from long-term treatment with calcium channel blockers. 

A paradoxical increase in pulmonary vascular resistance has been reported after intravenous infusion of glyceryl trinitrate, and care is needed when giving potent vasodilators to patients with idiopathic pulmonary hypertension (91). 

Adrie C, Ichinose F, Holzmann A, Keefer L, Hurford WE, Zapol WM. 1998. Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension. J. Appl. Physiol. 84 435 41... 

The cyclo-oxygenase metabolite prostacyclin is a potent, short-lived vasodilator and antithrombotic agent. Intravenous administration of the commercially available form of prostacyclin, epoprostenol, relieves the symptoms of primary pulmonary hypertension by dilating the pulmonary vasculature [99]. A stable prostacyclin analogue, iloprost, appears to be similarly effective when administered as an aerosol and obviates the logistical problems associated with maintained intravenous administration [100]. 

Hydralazine is the first systemic vasodilator drug advocated for initial treatment in patients with primary pulmonary hypertension. Rubin and Peter (1980) reported that short-term and long-term administration of hydralazine (200-300 mg/day) improved hemodynamics during rest and exercise in patients with primary pulmonary hypertension. The use of hydralazine, however, is not without hazard. In one study with 13 patients (Danahy et al., 1979), hydralazine produced only modest decreases in pulmonary arteriolar resistance and serious adverse effects that included hypotension (resulting in one death), renal insufficiency, and systemic arterial hypoxemia. 

Oral isosorbide dinitrate has been added to the list of vasodilator agents used for the treatment of primary pulmonary hypertension. In one study... 

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