Human vascular smooth muscle cells produce an intracellular form of interleukin-1 receptor antagonist.

Interleukin-1 (IL-1) is a proinflammatory monocyte- and macrophage-derived cytokine that has potent vasorelaxant effects on vascular smooth muscle cells (VSMC). VSMC themselves also express both IL-1 alpha- and beta-genes, suggesting that IL-1 may be an autocrine regulator of VSMC function. The present study demonstrates that human saphenous vein VSMC (HSVSMC) produce IL-1 receptor antagonist (IL-1Ra), a specific inhibitor of IL-1 action.

Interleukin 1 induces prostacyclin-dependent increases in cyclic AMP production and does not affect cyclic GMP production in human vascular smooth muscle cells.

Interleukin 1 (IL-1) is a pro-inflammatory cytokine which has direct vasorelaxant effects on vascular smooth muscle cells (VSMC). In the present study, IL-1 markedly increased intracellular levels of the vasodilatory mediator, cAMP, in human saphenous and human aortic VSMC. IL-1-induced cAMP was associated with a marked increase in prostacyclin (PGI2) production, and was reversed by indomethacin and tranylcypromine, inhibitors of cyclooxygenase and PGI2 synthetase respectively.

Interleukin 1 activates soluble guanylate cyclase in human vascular smooth muscle cells through a novel nitric oxide-independent pathway.

Recent demonstration of cytokine-inducible production of nitric oxide (NO) in vascular smooth muscle cells (VSMC) from rat aorta has implicated VSMC-derived NO as a key mediator of hypotension in septic shock. Our studies to determine whether an inducible NO pathway exists in human VSMC have revealed a novel cytokine-inducible, NO-independent pathway of guanylate cyclase activation in VSMC from human saphenous vein (HSVSMC). Interleukin 1 (IL-1), tumor necrosis factor (TNF), interferon gamma (IFN-gamma) and Escherichia coli lipopolysaccharide (LPS) increased cGMP at 24 h, whereas IL-2 and IL-6 were ineffective.

Plasma cyclic AMP and blood lactate responses to incremental cycling in untrained male subjects.

Recently, it has been suggested that epinephrine influences blood lactate and the lactate threshold during incremental exercise through a beta-adrenergic adenylate cyclase dependent mechanism. We sought to characterize the relationship between the changes in the beta-adrenergic adenylate cyclase system and blood lactate during incremental exercise indirectly through the measurement of plasma cAMP. The relationships of plasma cAMP to blood lactate levels and the lactate threshold were examined in nine untrained male subjects.

A comparison of the blood lactate and plasma catecholamine thresholds in untrained male subjects.

The relationships between the plasma epinephrine threshold (TE), the norepinephrine threshold (TNE), and the blood lactate threshold (Tlact) were examined during incremental cycling in 10 untrained male subjects. When oxygen uptake (VO2) measured at each threshold was expressed as a percent of VO2max, the thresholds occurred at 40.8 +/- 2.