calcimycin and Hypertrophy

The management of sick newborn infants who have sustained a hypoxic insult is a common clinical problem but relatively little is known about the recovery process. The aim of this study was to investigate this process in newborn piglets.. Thirty five newborn piglets were exposed to chronic hypobaric hypoxia for three days, either from birth, three or 14 days of age, and were allowed to recover for one, three, or six days. Control animals of relevant age were also studied. The heart weight ratio and pulmonary arterial muscularity were measured. Endothelial dependent and independent relaxation of the isolated intrapulmonary conduit arteries was determined in classical organ chamber studies, together with measurement of basal and stimulated cGMP accumulation.. After six days of recovery the hypoxia induced right ventricular hypertrophy and pulmonary arterial medial hypertrophy had decreased in all animals but values were still abnormal in the two younger age groups. Relaxation was still impaired during the first three days of recovery in all groups, had normalised by six days in the two youngest groups, but relaxation (both endothelium dependent and independent) remained impaired in older animals. In these older animals basal nitric oxide (NO) production and basal and stimulated cGMP accumulation was normal.. The recovery of the smooth muscle cells lags behind that of the endothelial cells. A normal stimulated increase in cGMP with reduced relaxation suggests an altered threshold for cGMP effected relaxation. These findings help to explain why some hypoxic infants require protracted NO therapy.

Topics: Acetylcholine; Animals; Animals, Newborn; Calcimycin; Cyclic GMP; Enzyme Inhibitors; Hypertension, Pulmonary; Hypertrophy; Hypertrophy, Right Ventricular; Hypoxia; Nitric Oxide; omega-N-Methylarginine; Phosphodiesterase Inhibitors; Pulmonary Artery; Purinones; Swine; Tunica Intima; Vasoconstriction; Vasodilator Agents

Bladder outlet obstruction (BOO) is a common disorder that is associated with altered bladder structure and function. For example, it is well established that BOO results in hypertrophy and hyperplasia of the bladder smooth muscle as well as detrusor instability. Since prostaglandins (PGs) and cyclic nucleotides (cyclic AMP [cAMP] and cyclic GMP [cGMP]) mediate both smooth muscle tone and proliferation, it is reasonable to suggest that changes in their levels may be involved in the pathophysiology of BOO-associated bladder disorders. Hence, the objective of this study was to investigate cyclic AMP, cyclic GMP and prostaglandins in the bladder of a rabbit model of BOO. BOO was induced in adult male New Zealand White rabbits. After 3 weeks, urinary bladders were excised, weighed and cut into segments. They were then incubated with stimulators of PGs, cAMP and cGMP and the formation of PGs, cAMP and cGMP were measured using radioimmunoassays. There was a significant increase in the obstructed bladder weights (P=0.002). The formation of PGE2, PGI2, cAMP and cGMP was significantly diminished in the detrusor (P<0.05) and bladder neck (P<0.05) in the BOO bladders compared to age-matched controls. Since PGE2, PGI2, cAMP and cGMP are known to inhibit the proliferation of smooth muscle cells (SMCs), the decreased synthesis of these factors, in BOO, may play a role in bladder SMC hypertrophy/hyperplasia. Our study points to the possible use of drugs that modulate the NO-cGMP and/or PG-cAMP axes in BOO-associated bladder pathology.

Topics: Acetylcholine; Animals; Calcimycin; Cyclic AMP; Cyclic GMP; Dinoprostone; Disease Models, Animal; Epoprostenol; Hyperplasia; Hypertrophy; In Vitro Techniques; Male; Muscle, Smooth; Organ Size; Phorbol 12,13-Dibutyrate; Prostaglandins; Rabbits; Urinary Bladder; Urinary Bladder Neck Obstruction

Stimulation of ornithine decarboxylase (ODC) activity was examined in cultured heart cells from neonatal rats. Fetal bovine serum had a concentration-dependent effect on ODC activity with maximum response obtained at 10% serum. ODC activity peaked 4 h after the addition of serum and returned to initial levels at 8 h. In the absence of serum, non-cytotoxic concentrations of the adrenergic agonists epinephrine, norepinephrine or isoproterenol did not stimulate ODC activity. Co-administration of serum and catecholamines at 10(-5) M induced an ODC response that was significantly greater than that induced by serum alone. A screen of various constituents of serum revealed that insulin, though relatively ineffective alone, acted cooperatively with catecholamines to produce an ODC response equivalent to that induced by 10% serum. Propranolol effectively blocked the cooperative effect of insulin on catecholamine stimulation of ODC activity, and markedly inhibited the stimulation of ODC by 10% serum. Insulin also acted cooperatively with the second-messenger analogue dibutyryl-cAMP. The calcium ionophore A23187 significantly increased ODC activity and this response was potentiated by the presence of insulin. The present findings are concordant with in vivo observations in that beta-adrenergic activation stimulates ODC activity in cultured heart cells, but it also demonstrates that the cooperative action of other factors present in serum, such as insulin, are required.

Topics: Animals; Blood Proteins; Calcimycin; Cardiomegaly; Catecholamines; Cells, Cultured; Cyclic AMP; Drug Synergism; Fibroblasts; Heart; Hypertrophy; Insulin; Isoproterenol; Myocardium; Ornithine Decarboxylase; Rats