Bronchodilator, cardiovascular, and cyclic guanylyl monophosphate response to high-dose infused atrial natriuretic peptide in asthma.
Atrial natriuretic peptide (ANP) has bronchodilator and vasodilator properties thought to be mediated through the generation of cyclic guanylyl monophosphate (cGMP). The current study was designed to examine the effects of infused ANP on respiratory (FEV1), cardiovascular (blood pressure and pulse), and metabolic (plasma cGMP) function in asthmatic patients. Eight patients with a mean +/- SD age of 45.6 +/- 8.2 yr and mean FEV1 of 56.4 +/- 15.4% of predicted were studied using a randomized double-blind crossover design. On one study day after baseline measurements (FEV1, blood pressure, pulse, and plasma cGMP), ANP was infused for 20-min periods at 5 pmol/kg/min and at 25 pmol/kg/min; a placebo (saline) inhalation was then administered. On the other day the placebo infusion was followed by inhalation of 5 mg albuterol. Measurements were repeated at the end of each 20-min period. The highest rate of ANP infusion increased the FEV1 by 0.50 +/- 0.09 L compared with 0.09 +/- 0.05 after the placebo infusion (p < 0.001). The increase in FEV1 produced by ANP plus placebo inhalation (0.50 +/- 0.28 L) was similar to that produced by placebo infusion plus albuterol inhalation (0.61 +/- 0.30 L). There was no clinically significant fall in systolic or diastolic blood pressure (torr) at the 25 pmol/kg/min infusion rate. The mean basal cGMP was 602 +/- 242 fmol/ml and increased to 5,883 +/- 1,460 and 21,182 +/- 2,509 with the two rates of ANP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Angus
R M
RM
Department of Respiratory Medicine, Western Infirmary, Glasgow, Scotland.
McCallum
M J
MJ
Hulks
G
G
Thomson
N C
NC
D000328:Adult; D000420:Albuterol / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D006152:Cyclic GMP / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011674:Pulse / Q000187:drug effects
D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D000420:Albuterol