Endogenous nitric oxide as a probable modulator of pulmonary circulation and hypoxic pressor response in vivo

Abstract

The objective of this study was to investigate the role of endogenous nitric oxide, formed from L-arginine, in the regulation of pulmonary circulation in vivo, with special reference to the hypoxic pressor response. In artificially ventilated open-chest rabbits, pulmonary vascular resistance at normoxic ventilation (FIO2 = 21%) was 78 +/- 16 cmH2O ml-1 min 1000-1 (mRUL). Hypoxic ventilation (FIO2 = 10%) increased pulmonary vascular resistance to 117 +/- 17 mRUL. N omega-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased pulmonary vascular resistance at normoxic ventilation to 192 +/- 28 mRUL and during hypoxic ventilation to 462 +/- 80 mRUL. During N omega-nitro-L-arginine methylester infusion there was also an increase in mean arterial blood pressure as well as a decrease in cardiac output that was even more pronounced during hypoxic ventilation. L-arginine reversed the effect of N omega-nitro-L-arginine methylester on pulmonary vascular resistance at normoxic ventilation to 140 +/- 26 mRUL and at hypoxic ventilation to 239 +/- 42 mRUL. In spontaneously breathing closed-chest rabbits, N omega-nitro-L-arginine methylester evoked a marked decrease in arterial PO2 and increases in respiration frequency and central venous pressure, while blood pH, PCO2 and base excess remained unchanged. Taken together these findings indicate that endogenous nitric oxide, formed from L-arginine, might be a regulator of ventilation-perfusion matching at normoxic ventilation, and that nitric oxide acts as an endogenous modulator of the hypoxic pressor response.

Role of Nitric Oxide Synthase and Cyclooxygenase in Pulmonary Vascular Control in Isolated Perfused Lungs of Ferrets, Rats and Rabbits

“…Cremona et al (1994) who used a similar preparation, also found that ¬_NAME did not alter pulmonary vascular resistance (PVR) during normoxia in dog lungs but raised it in the lungs of sheep, pigs and humans; in all four species, ¬_NAME raised pulmonary vascular resistance during hypoxic vasoconstriction (HPV). In rabbits, in vivo, Persson et al (1990) and, in intact cats Hyman et al McMahon et al (1991) found that NOS blockade raised Ppa during normoxia. However, in conscious dogs, Nishiwaki et al (1992) found no evidence that NO was released in the absence of experimental stimuli.…”

Comparison of the ability of nicardipine, theophylline and zaprinast to restore cardiovascular haemodynamics following inhibition of nitric oxide synthesis

“…A fall in cardiac output has also been observed in human subjects receiving NO synthase inhibitors (Petros et al, 1991) or the guanylate cyclase inhibitor, methylene blue (Schneider et al, 1992) as treatment for septic shock resulting in limitation of their use to treat this condition. The reason for the fall in cardiac output is unknown although increased afterload (Gardiner et al, 1990;Persson et al, 1990), reduced preload (Persson et al, 1990) direct myocardial action (Gardiner et al, 1990;Persson et al, 1990;Schulz et al, 1992), coronary vasoconstriction (Gardiner et al, 1990;Persson et al, 1990;Amrani et al, 1992;Schulz et al, 1992) and activation of baroreceptor reflexes (Kilbourn et al, 1990) have all been suggested. Inhibition of endocardial (Schulz et al, 1991) or myocardial (Schulz et al, 1992) NO synthesis are further potential mechanisms.…”

The vasoconstrictor effects of L‐NAME, a nitric oxide synthase inhibitor, in pregnant rabbits

“…However, inhibition of NO synthesis induces vasoconstriction not only in the systemic, but also in the pulmonary (Persson et al, 1990;Perrella et al, 1991) and cor-onary (Amezcua et al, 1989) heart rate (HR, 1 min-') were monitored through a cannula containing 50 u heparin ml-' NaCl which was inserted into the right femoral artery. The cannula was connected to a pressure transducer (BRP-01, Experimetria, Budapest, Hungary) and a blood pressure coupler (HG-02, Experimetria).…”