Developmental Changes in Adenylate Cyclase Activity in Canine Myocardium

Abstract

Basal and epinephrine-induced adenylate cyclase activity in homogenates of dog myocardium increased significantly from birth to adulthood, without further change with advancing age. The stimulatory effect of epinephrine (i.e. the net increase over basal activity), however, increased (p < 0.05) during the first week after birth only and then remained constant. While fluoride-stimulated activity increased, 5'-guanylyl imidodiphos- phate [Gpp(NH)p]-stimulated activity declined gradually during development (p < 0.05). In the presence of Gpp(NH)p and epinephrine at concentrations producing a maximal effect, the enzyme activities in all dogs, except in the 1-day-old, were not significantly different and were comparable to that of fluoride-stimulated activity in adult dogs. The results suggest that age-related alterations in the characteristics of the guanine nucleotide regulatory protein may account, at least in part, for the changes in adenylate cyclase activity occurring during development.

Milrinone Effects in the Isolated Immature Rabbit Heart

“…tant differences between immature and adult myocardium, which might help explain agerelated changes in contractility. These devel opmental differences include: lower intracel lular calcium concentration [15], decreased adenylate cyclase activity [16], decreased myofibrillar content [17], decreased myofi brillar ATPase activity [18], immaturity and decreased quantity of sarcoplasmic reticulum [19] , and differences in myosin isoenzymes [20] , For isoproterenol, the mechanism of action is mediated by the ß-receptor. This receptor has been noted to be reduced in num ber in the immature heart [21], Although these developmental features may explain the decreased sensitivity of newborns to ino tropic stimulation, it is pertinent to note that the contractile proteins from immature and adult myocardium appear to be equally sensi tive to calcium stimulation [22], This latter finding suggests that the failure of the stan dard inotropic drugs in the immature heart is due to a relative inability to increase intracel lular calcium.…”

Developmental Differences in the Electrophysiological Response of Isolated Canine Purkinje Fibers to Adrenergic Stimulation during Simulated Ischemia

“…We used young dogs of 0-21 days of age because studies suggest that maturational dif ferences in the canine cardiac response to stel late ganglion stimulation [22,23], reflex-me diated sympathetic effects [24,25], and iso proterenol effects [26] persist well beyond this developmental age. The developmental dif ferences in basal and fluoride-stimulated ade nylate cyclase [27], norepinephrine content of the heart [28], and some cellular electrophysiological differences [29,30] also persist beyond 21 days of age. While we did not see the less negative membrane potential some times reported for neonates, we do not believe this to be a function of including animals up to 21 days of age.…”