We established that an increase in dysponea-free duration of exercise in mitral stenosis patients after percutaneous mitral valvulotomy which lowers their raised left atrial pressures and pulmonary congestion, was the reduction of juxtapulmonary capillary (J) receptor stimulus and so of their reflex effects (Anand et. al., 2009) which are to accelerate breathing and limit physical activity (Paintal, 1969). In humans they can be also stimulated chemically by lobeline (Raj,et.al., 1995; Anand et al.,2010). With a view to substantiating this conclusion we studied patients with Eisenmenger syndrome (ES). ES is characterized by both a high pulmonary artery pressure and raised pulmonary vascular resistance index due to a ventricular septal defect which also leads to a fall in arterial oxygen saturation (SaO2). The studies conformed to the Helsinki Declaration and were approved by the ethical committee of All India Institute of Medical Sciences. The protocols involved (i) distance covered in a 6-min walk test (6MWT) (ii) duration of exercise according to a modified Bruce Protocol limited by discomfort or a 20%fall in SaO2 (iii) threshold dose of lobeline for eliciting respiratory sensations. Responses were restudied after 6 weeks of medication with sildenafil (3mg TDS), a phosphodiesterase type-5 inhibitor and a preferential pulmonary vasodilator. After medication the mean (estimated) pulmonary artery systolic pressure fell from 104.5±4.18 to 90.6±2.8 mmHg (P= 0.0001);resting SaO2 which was 89.8± 1.2 mmHg remained unchanged at 89.8± 0.86 mmHg;distance covered in 6MWT increased from 487.5± 44.9 to 551.25±39.0 meters (P=0.0001) and the mean duration of exercise increased from 8.26±0.9 to 10.47±1.06 min (P=0.002), demonstrating a significant improvement in their symptomatic status. Threshold dose of lobeline i.v. gave rise to exercise-related respiratory sensations and decreased significantly from 37.5±3.4 to 20.3±1.8µg/kg (P=0.001). A fall in lobeline-sensation dose indicates a fall in pulmonary vascular resistance; the latter having been reported with oral tadalafil, also a phosphodiesterase type-5 inhibitor (Mukhopadhyay et al.,2006). Since a reduction in pulmonary vascular resistance with these drugs constitutes a reduction in stimulus to J receptors, their reflexes which are the patients symptoms, will also be attenuated.SaO2 remained unchanged with sildenafil medication for up to 6 weeks and appears to play an insignificant role in the patient’s clinical improvement.