Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)
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Proc. Soc. Exp. Biol. Med. · Feb 1995
In vivo administration of endotoxin and tumor necrosis factor-alpha produce different effects on constitutive and inducible nitric oxide synthase activity in rat neutrophils and aorta ex vivo.
Tumor necrosis factor-alpha (TNF-alpha) inhibits release of nitric oxide (NO) in vitro by stimulating the degradation of constitutive NO synthase (cNOS III) mRNA. However, TNF-alpha is believed to be the cytokine mediator of the hypotension and upregulation of inducible NO synthase (iNOS II) produced by gram-negative bacterial endotoxin (LPS). Some in vivo effects of TNF-alpha are opposite to those which occur in vitro. ⋯ However, TNF-alpha mediates in part LPS-induced inhibition of RNI production by RTA. Thus, endogenous TNF-alpha is not required for LPS-induced acute phase hypotension or iNOS II activity. The importance of TNF-alpha in sepsis resides in systems other than iNOSII and blood pressure.
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Proc. Soc. Exp. Biol. Med. · Feb 1994
Cerebral vascular response to hemorrhagic hypotension in newborn lambs: the influence of developing anemia.
The ability of newborn animals to autoregulate cerebral blood flow (CBF) has been documented. Most studies of the cerebral vascular response to hypotension utilize hemorrhage, generally confounded with anemia. We studied the cerebral blood flow and metabolic response of chloralose and urethane anesthetized newborn lambs to regulated hypotension. ⋯ Calculated oxygen consumption was maintained in the AH group but increased (approximately 50%) in the NH group at 50 and 40 mm Hg. The ratio of oxygen uptake to oxygen delivery (fractional oxygen extraction) increased linearly in both groups as arterial pressure decreased. The major findings of these experiments are (i) The anesthetized newborn lamb can maintain CBF when perfusion pressure falls to 25 mm Hg and this autoregulatory capacity (classically defined) is not dependent on a change in hematocrit and, presumably, viscosity; (ii) Cerebral hypotension, anemic or not, appears to be accompanied by an increase in fractional extraction of oxygen.
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Proc. Soc. Exp. Biol. Med. · Oct 1990
Digitalis attenuates arterial hypertrophy in experimental hypertension.
Several investigators have reported that digitalis administration reduces cardiac hypertrophy in rats with experimental hypertension. To determine whether digitalis similarly affects growth of arteries, we studied young (5- to 14-week-old), male, one-kidney, one-clip hypertensive rats (1K1C; n = 14) and one-kidney normotensive control rats (1K; n = 26). Half of the rats received digoxin (150 mg/kg body wt/day) in chow starting 1-2 weeks before clipping (1K1C-D; 1K-D); the other half were pair-fed (1K1C-C; 1K-C). ⋯ As compared with pooled normotensive control rats, femoral arterial pressure (1K1C-D, 165 +/- 8; 1K1C-C, 153 +/- 5), aortic water content (1K1C-D, 64.8 +/- 0.4; 1K1C-C, 64.9 +/- 0.5), and aortic weight (1K1C-D, 44.8 +/- 2.1; 1K1C-C, 50.1 +/- 1.6) were increased (P less than 0.001) in the one-kidney, one-clip rats, on or off digoxin. Comparison of hypertensive rats receiving to those not receiving digoxin revealed no differences in arterial pressure or aortic water content, but aortic growth was significantly attenuated (-41%, P = 0.02) in the hypertensive rats receiving digoxin. These results provide evidence that digoxin reduces hypertensive arterial growth by a mechanism that does not affect normal growth.
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Proc. Soc. Exp. Biol. Med. · May 1989
Increased plasma levels of platelet-derived growth factor activity in patients with progressive systemic sclerosis.
We measured mitogenic activity of whole blood serum and platelet-poor plasma-derived serum of a group of 10 patients with progressive systemic sclerosis and of 8 controls. Mitogenic activity of plasma-derived serum was greater in patients than in controls, in the absence of other signs of platelet activation. This increased activity was inhibited by specific antibodies, anti-platelet derived growth factor, suggesting that circulating levels of platelet-derived growth factor may be present in progressive systemic sclerosis patients. Platelet-derived growth factor, released either by platelets or by monocytes, might play a role in the pathogenesis of scleroderma.
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Proc. Soc. Exp. Biol. Med. · May 1989
Peptidergic modulation of efferent sympathetic neurons in intrathoracic ganglia regulating the canine heart.
When either substance P or vasoactive intestinal peptide was injected into an acutely decentralized intrathoracic sympathetic ganglion, short-lasting augmentation of cardiac chronotropism and inotropism was induced. These augmentations were induced before the fall in systemic arterial pressure occurred which was a consequence of these peptides leaking into the systemic circulation in enough quantity to alter peripheral vascular resistance directly. When similar volumes of normal saline were injected into an intrathoracic ganglion, no significant cardiac changes were induced. ⋯ Following the intravenous administration of naloxone, the positive inotropic cardiac responses induced by efferent preganglionic sympathetic axonal stimulation were enhanced minimally in control states and significantly following hexamethonium administration. Thus, it appears that enkephalins are involved in the modulation of intrathoracic ganglion neurons regulating the heart, perhaps via modification of beta-adrenergic receptors. Taken together these data indicate that substance P, vasoactive intestinal peptide, neuropeptide Y, or enkephalins modify intrathoracic ganglionic neurons which are involved in efferent sympathetic cardiac regulation.