ONTOGENY OF DRY GAS HYPERPNEA-INDUCED BRONCHOCONSTRICTION IN GUINEA-PIGS

Ontogeny of dry gas hyperpnea-induced bronchoconstriction in guinea pi gs. J. Appl. Physiol. 76(3): 1150-1155, 1994. - Adolescent guinea pigs (AGPs) demonstrate dry gas hyperpnea-induced bronchoconstriction (HIB ) that shares key features with HIB in humans with asthma. The airways of immature animals exhibit enhanced reactivity to diverse types of s timulation. We tested whether dry gas HIB is also increased in newborn guinea pigs (NGPs). We quantified HIB as the fractional increase of r espiratory system resistance (Rrs) over baseline (BL) in five 4- to 7- day-old NGPs after 10 min of hyperpnea, as well as changes in Rrs elic ited by intravenous methacholine or capsaicin, and compared these resp onses with those of AGPs. During hyperpnea, analogous stimuli were del ivered by mechanically imposing hyperpnea at 3.0, 4.5, and 6.0 times q uiet eucapnic minute ventilation (VE). In AGPs, hyperpnea caused signi ficant bronchoconstriction that increased with ire; peak fractional in crease of Rrs was 7.6 +/- 2.0 times BL. In contrast, hyperpnea caused insignificant bronchoconstriction in NGPs (1.4 +/- 0.2 times BL after the largest VE; P < 0.05 vs. AGP). Responses elicited by methacholine (10(-10)-10(-7) mol/kg) or capsaicin (0.01-10.0 mu g/kg) were similar in NGPs and AGPs. In AGPs, hyperpnea suppressed HIB until posthyperpne a. To determine whether the reduced HIB of hTGPs was caused by enhance d suppression, NGPs and AGPs were administered acetylcholine (10(-10)- 10(-7) mol/kg iv) during BL eucapnic ventilation and during eucapnic h yperpnea with warm humidified gas. Responses to acetylcholine were sup pressed in AGPs and NGPs to a similar degree. We conclude that HIB is markedly diminished shortly after birth in guinea pigs and that it inc reases substantially during maturation. Reduced HIB in NGPs is not cau sed by inadequate airway contractility or inadequate sensorimotor func tion nor by increased hyperpnea suppression of bronchoconstriction.