Biomedical subjects

W S Colucci

Publications and source records attributed to W S Colucci.

167 records · Page 10Linked to original sources

PubMed1977

Tetracycline-induced pleural symphysis for recurrent hydrothorax complicating cirrhosis. A new approach to treatment.

Two patients with cirrhosis and ascites complicated by extensive unilateral pleural transudates refractory to therapy with dietary sodium restriction, diuretics, and repeated thoracentesis were successfully managed by tetracycline-induced pleural symphysis. The intrapleural instillation of this antibiotic prevented the recurrence of the effusion and substantially relieved the patients' symptoms with minimal undesirable side effects.

Female↗

PubMedDate not supplied

Role of nitric oxide in the regulation of myocardial function.

Nitric oxide (NO), produced by either constitutive or inducible isoforms of NO synthase (cNOS or iNOS), influences myocardial inotropic and chronotropic responses. This pathway has been studied using NO donors or NOS inhibitors or by immune-mediated stimulation of iNOS. Although inhibition of constitutive NO activity in the heart does not influence indices of myocardial contractility, NO donors, in some species and preparations, may exert a negative inotropic effect as well as an enhancement of diastolic relaxation. The best documented cardiac action of NO is inhibition of the positive inotropic and chronotropic responses to beta-adrenergic receptor stimulation. Basal NO production, presumable via cNOS, appears to exert a mild tonic inhibition of beta-adrenergic responses. On the other hand, excessive NO production mediated by iNOS may contribute to the myocardial depression and beta-adrenergic hyporesponsiveness associated with conditions such as sepsis, myocarditis, cardiac transplant rejection, and dilated cardiomyopathy. Muscarinic cholinergic stimulation of the heart appears to stimulate NO production that mediates, at least partially, parasympathetic slowing of heart rate and inhibition of beta-adrenergic contractility. NO-stimulated production of 3',5'-cyclic guanosine monophosphate via guanylyl cyclase accounts for many of the observed physiological actions of NO. 3',5'-Cyclic guanosine monophosphate inhibits the beta-adrenergic-stimulated increase in the slow-inward calcium current and reduces the calcium affinity of the contractile apparatus, actions that could contribute to a negative inotropic effect, an abbreviation of contraction, and an enhancement of diastolic relaxation. Biochemical, immunocytochemical, and molecular biological techniques have been used to show the presence of both cNOS and iNOS within the myocardium. cNOS is expressed in myocytes, endothelial cells, and neurons in the myocardium, and there is evidence for iNOS in myocytes, small vessel endothelium, vascular smooth muscle cells, and immune cells that infiltrate the heart. Taken together, these observations suggest that NO influences normal cardiac physiology and may play an important role in the pathophysiology of certain disease states associated with cardiac dysfunction.

Animals↗

PubMedDate not supplied

Role of endothelin-1 in myocardial failure.

Endothelin-1 (ET-1) is a potent molecule produced throughout the cardiovascular system; it can exert important effects on both the structure and function of vascular smooth muscle cells and cardiac myocytes. ET-1 appears to play a central role in the physiological regulation of cardiovascular function, particularly in the vasculature. The known actions of ET-1 and the demonstration that plasma ET-1 is elevated in patients with heart failure has raised the possibility that this molecule could play a role in the pathophysiology of heart failure. This thesis has been supported and furthered by studies in animal models of heart failure that demonstrate the salutary, short-term effects of ET-1 receptor antagonists on hemodynamic function, as well as improved ventricular remodeling and survival with long-term administration. Early clinical trials with these ET receptor blockers have demonstrated systemic vasodilation. Long-term trials to determine the effects of ET-1 blockade on symptoms and survival are under way.

Animals↗

PubMedDate not supplied

Characterization of postsynaptic alpha-adrenergic receptors by [3H]-dihydroergocryptine binding in muscular arteries from the rat mesentery.

Alpha-adrenergic receptors are likely to be important determinants of the effects of catecholamines on vascular resistance. To study the alpha-adrenergic receptor in muscular arteries of the type that determine vascular resistance, we characterized and quantitated alpha-adrenergic receptors in a particulate fraction of the highly reactive, richly innervated arteries of the rat mesentery. With the ligand [3H]-dihydroergocryptine ([3H]-DHEC), specific binding (displaceable by 5 microM phentolamine) is saturable. There is a single class of binding sites with a dissociation constant (Kd) of 2.9 nM and a maximal binding capacity of 68 fmoles of [3H]-DHEC per mg of particulate fraction protein. Catecholamines compete for [3H]-DHEC binding stereospecifically and with the alpha-adrenergic potency series of (-)epinephrine greater than (-)norepinephrine greater than (-)isoproterenol. Binding is rapid (t 1/2 less than or equal to 2 mins) and rapidly reversible (t 1/2 less than or equal to 2 mins). Inhibition of [3H]-DHEC binding by the alpha-adrenergic antagonist phentolamine (Kd = 3.0 nM) is much greater than by the beta-adrenergic antagonist propranolol (Kd = 8200 nM). The alpha 1-selective antagonist prazosin (Kd = 63 nM) is 20 times more potent in competing for [3H]-DHEC binding than is the alpha 2-selective antagonist yohimbine (Kd = 1250 nM), thus suggesting that the alpha-adrenergic receptor identified is predominantly of the alpha 1 subtype that is responsible for vascular smooth muscle contraction. This extension of radioligand binding techniques to highly innervated muscular arteries of the type contributing to vascular resistance will allow the study of the role of the vascular alpha-adrenergic receptor in various physiologic states and models of hypertension.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Regulation of alpha 1-adrenergic receptor-coupled calcium flux in cultured vascular smooth muscle cells.

To study the role of the alpha-adrenergic receptor (AAR) pathway in the regulation of catecholamine-induced vascular contraction, we developed methods for the direct evaluation of AAR and AAR-coupled calcium efflux in cultured vascular smooth muscle cells derived from the rabbit aorta by enzymatic dissociation. AAR were characterized by the binding of the alpha 1- and alpha 2-selective radioligands [3H]-prazosin and [3H]-yohimbine, respectively. Norepinephrine-stimulated efflux of 45calcium from preloaded cells was measured as an index of AAR-mediated calcium flux. The [3H]-prazosin binding was of high affinity (Kd = 0.15 nM), saturable (Bmax = 75-125 fmol/mg protein), and competed for by agonists and antagonists in the order expected for an alpha 1 receptor. There was no specific binding of [3H]-yohimbine. Norepinephrine-stimulated 45Ca efflux was concentration-dependent (EC50 congruent to 100 nM), and potently blocked by prazosin (IC50 congruent to 0.1 nM), but not yohimbine (IC50 greater than 100 nM), indicating, together with the binding data, that norepinephrine-stimulated 45Ca efflux in this system is alpha 1 mediated. Following treatment of cells with 1-norepinephrine (0.1 nM) for 24 hours, the density of AAR and maximal norepinephrine-stimulated 45Ca efflux were decreased by 72% +/- 14% and 91% +/- 9%, respectively. This cultured cell system offers several advantages for study of the mechanisms of coupling and regulation of alpha-adrenergic receptors in vascular smooth muscle.

Animals↗