Effects of nitrendipine and hypoxia on pulmonary vascular resistance in experimental emphysema.
We evaluated the hemodynamic effects of nitrendipine, a dihydropyridine Ca2+ channel blocker, and hypoxia in intact dogs with emphysema produced by treatments with aerosolized papain. We also determined the effects of emphysema, chronic Ca2+ channel blocker treatment, and acute hypoxia on the distribution of vascular resistance in isolated left lower lobes. Pulmonary vascular resistance was increased (4 +/- 1 mm Hg/L/min) in the animals studied 6 months after receiving 4 weekly treatments with papain compared with control animals (2.6 +/- 0.6 mm Hg/L/min, p less than 0.05), and this effect of emphysema was blunted with chronic nitrendipine, 3 mg/kg twice a day (3.1 +/- 0.9 mm Hg/L/min). Both at baseline and at 6 months, hypoxia-induced increases in pulmonary vascular resistance were abolished by nitrendipine. The total pulmonary pressure gradient (delta Pt) was partitioned into pressure gradients across arterial (delta Pa), middle (delta Pm), and venous (delta Pv) vessels by occlusions performed during normoxia (PIO2 = 200 mm Hg) and hypoxia (PIO2 = 30 mm Hg). Papain-treated animals had elevated delta Pt compared with that in control animals because of an increased delta Pv (9.7 +/- 1.1 mm Hg versus 5.2 +/- 0.4 mm Hg in control animals, p less than 0.05). In contrast, only delta Pm was increased with papain + nitrendipine (2.6 +/- 1.0 mm Hg versus 0.2 +/- 0.3 mm Hg in control animals, p less than 0.05). An increase in the downstream pressure gradient was also observed when lobes from animals with emphysema were studied under conditions of reverse perfusion. Hypoxic responses were similar in the control and papain groups, with increases in delta Pa and delta Pm.(ABSTRACT TRUNCATED AT 250 WORDS)
Rubin
L J
LJ
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201.
Tod
M L
ML
Yoshimura
K
K
D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D004285:Dogs; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D009568:Nitrendipine / Q000494:pharmacology*; D010101:Oxygen Consumption; D010206:Papain; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects
D009568:Nitrendipine; D010206:Papain