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Angiotensm II stimulates secretion of corticosteroids and ouabam-like activity from adrenocortical cells Distmct adrenocortical angiotensm II receptor subtypes (AT,, AT*) have been described, and the present studies investigated their roles in steroid secretion Using pnmary bovine adrenocortlcal cell cultures under serum free conditions, anglotensm II stimulated the secretlons of aldosterone, cortisol, and endogenous ouabam as venfied by high-performance chromatography The dose-response curves for stimulated steroid secretion were parallel with unitary slopes while the half-maximally effective concentrations of angiotensm II were 0 31 to 0 38 nmol/L for secretions of aldosterone and cortisol and 2 3 nmol/L for endogenous ouabam The nonselective mammalian antagonist (Sar'-Ile') angiotensin II blocked stimulated secretion of all three steroids without affectmg basal output In the presence of the AT, antagonist DuP753, anglotensm II-stimulated secretions of aldosterone and cortlsol were blocked while secretion of endogenous ouabam was unaffected In the presence of the AT2 antagonist PD1233 19, both basal and angiotensm II-stimulated secretions of aldosterone and cortisol were normal while stimulated secretion of endogenous ouabam was mhibited The secretion of endogenous ouabam was activated maximally by the AT2 agonist CGP42112 under conditions m which aldosterone secretion was unaffected These results demonstrate that AT2 receptors stimulate secretion of endogenous ouabam from bovine adrenocortical cells The specsficity of AT, and AT, receptor stimulation mdicates that separate signaling mechanisms havmg rnnumal cross talk control the adrenocortical secretions of corticosteroids and cardiac-active steroids Adrenocortical AT2 receptors may be important m the adaptation to low salt diets and other conditions In which angiotensm II 1s increased (Hypertension. 1997 T he effects of anglotensm II (AII), the octapeptlde of the remn-angiotensin system, are mediated pnmarlly by angiotensm receptors present on the extracellular surface of target cells 1 The physiological actions of AI1 include the stlmulatlon of aldosterone secretlon from adrenocortlcal cells At least two different AI1 receptor subtypes, termed type 1 (AT,) and type 2 (AT,), have been Identified with the use of receptor antagomsts. Both receptor subtypes have been cloned,z-5 and the AT, subtype accounts for 80% of the angiotensm II receptors m the rat and bovine adrenal, the other 20% being the AT2 subtype.6$7Studies with ATI-and AT,-specific antagonists have shown that most of the known physiological effects of AII, mcludmg stimulation of adrenocortical steroid secretion, are medlated by the ATI receptor.* The physlologlcal role of the AT2 receptor in the adrenal gland 1s not known AT2 receptors have been shown to modulate T-type calcium channels m NG108-15 neuroblastoma/ glloma cells and synthesis of prostaglanchns in human astrocytes 9.10 In the rat zona glomerulosa and PC12W cells, stlmulatlon of AT2 receptors appears to reduce guanylate cyclas...

Intervertebral disc degeneration is a disease identified as an inflammation response-participated pathological process. As a classical cellular feature, disc cell senescence is reported to be closely related with disc cell senescence. Resveratrol has a protective role against inflammation in some cells. However, its biological effects on disc cells remain largely unclear. The present study was aimed to study the effects of resveratrol on disc nucleus pulposus (NP) cell senescence in an inflammation environment. Isolated NP cells were cultured in cultured medium with (control group) or without (inflammation group) inflammatory cytokine TNF-α and IL-1β for 14 days. Resveratrol was added along with the NP cells treated with inflammatory cytokines to investigate its effects. NP cell senescence was analyzed by senescence-associated β-Galactosidase (SA-β-Gal) staining, cell proliferation, G0/1 cell cycle arrest, telomerase activity, gene/protein expression of senescence markers (p16 and p53) and NP matrix biosynthesis. In addition, the intracellular reactive oxygen species (ROS) was also analyzed. Compared with the control group, inflammation group significantly increased SA-β-Gal activity and ROS content, decreased cell proliferation and telomerase activity, promoted G0/1 cell cycle arrest, up-regulated gene/protein expression of senescence markers (p16 and p53) and matrix catabolism enzymes (MMP-3, MMP-13 and ADAMTS-4), and down-regulated gene/protein expression of NP matrix macromolecules (aggrecan and collagen II). However, resveratrol partly reversed the effects of inflammatory cytokine on these cell senescence-associated parameters. Together, resveratrol was effective to suppress cell senescence in an inflammatory environment. The present study shows new knowledge on how to retard inflammation response-initiated disc degeneration.