Nitric oxide and pulmonary hypertension

Abstract

Pulmonary hypertension is a serious complication of a number of lung and heart diseases that is characterized by peripheral vascular structural remodeling and loss of vascular tone. Nitric oxide can modulate vascular injury and interrupt elevation of pulmonary vascular resistance selectively; however, it can also produce cytotoxic oxygen radicals and exert cytotoxic and antiplatelet effects. The balance between the protective and adverse effects of nitric oxide is determined by the relative amount of nitric oxide and reactive radicals. Nitric oxide has been shown to be clinically effective in the treatment of congenital heart disease, mitrial valvular disease combined with pulmonary hypertension and in orthotropic cardiac transplantation patients. Additionally, new therapeutic modalities for the treatment of pulmonary hypertension, phosphodiesterase inhibitors, natriuretic peptides and aqueous nitric oxide are also effective for treatment of elevated pulmonary vascular resistance.

Keywords: Nitric oxide; Pulmonary hypertension; Pulmonary vascular resistance.

Fig. 1

Major mechanisms causing pulmonary hypertension.

Fig. 2

Schematic diagram showing the proposed mechanism for activation of soluble guanylate cyclase by nitric oxide.

Fig. 3

Mechanisms of nitric oxide/cGMP-induced vasodilation. VOCC: voltage-operated calcium channels, ROCC: receptor-operated calcium channels, SERCA: sarcoplasmic/endoplasmic reticulum Ca2+ATPase, IP3 channel: inositol 1,4,5-trisphosphate-gated calcium channel, [Ca2+]i: intra cellular free calcium ion concentration.

Fig. 4

Schematic representation of the cGMP pathway that mediates vasodilation and inhibition of cellular proliferation of drugs.