NEUROPEPTIDE-Y INFUSION IMPROVES HEMODYNAMICS AND SURVIVAL IN RAT ENDOTOXIC-SHOCK

被引:23
作者
HAUSER, GJ [1 ]
MYERS, AK [1 ]
DAYAO, EK [1 ]
ZUKOWSKAGROJEC, Z [1 ]
机构
[1] GEORGETOWN UNIV, DEPT PHYSIOL & BIOPHYS, WASHINGTON, DC 20007 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1993年 / 265卷 / 04期
关键词
SEPTIC SHOCK; NOREPINEPHRINE; VASOCONSTRICTION; HYPOTENSION; ENDOTOXIN; ADRENERGIC BLOCKADE; PHENTOLAMINE;
D O I
10.1152/ajpheart.1993.265.4.H1416
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Neuropeptide Y (NPY), a sympathetic and platelet-derived vasoconstrictor, acts both directly and by potentiating adrenergic responsiveness and therefore may be beneficial in endotoxic shock, where suppressed vascular responsiveness to adrenergic agents is a key factor. This was studied in anesthetized rats. First, infusion of a nonhypotensive dose of endotoxin (lipopolysaccharide, LPS) markedly suppressed the pressor response to increasing doses of norepinephrine (NE), angiotensin II, and vasopressin but did not suppress the response to NPY. Second, in rats rendered hypotensive by intravenous LPS, continuous NE infusion (0.1-1.0 mug-kg-1.min-1 started 5 min after LPS for 1 h) did not alter hemodynamics. In contrast, 5 nmol.kg-1.min-1 of NPY (equipotent to 0.1 mug.kg-1.min-1 of NE in normal rats) increased mean arterial pressure (MAP, from 64 to 114% of baseline), total peripheral resistance index (TPRI, from 64 to 154% of baseline), and left ventricular stroke work index (from 36 to 73% of baseline), without changing cardiac index (CI). Third, in a similar experimental protocol, pretreatment of the hypotensive rats with phentolamine blocked the pressor effect of NE infusion, but only partially attenuated the response to NPY. Finally, addition of low-dose NPY to NE infusion improved survival following a lethal dose of LPS compared with treatment with NE alone (P < 0.01). Thus, unlike other vasoconstrictors tested, NPY-mediated vasoconstriction is preserved during endotoxemia. The beneficial effect of NPY is mediated by increased TPRI without reduction in CI; both NPY receptor-mediated vasoconstriction and potentiation of adrenergic responsiveness may be involved.
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页码:H1416 / H1423
页数:8
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