RESISTANCE TO ENDOTOXIN-SHOCK IN SPONTANEOUSLY HYPERTENSIVE RATS

Septic shock involves systemic vasodilation mediated by proinflammator y cytokines. In essential hypertension, vascular and immune dysfunctio ns are closely associated. The response of hypertensive animals compar ed with normotensive controls to endotoxin (lipopolysaccharide; LPS) c hallenge is not known. Age-matched (12 weeks) normotensive Wistar-Kyot o rats (WKY) and spontaneously hypertensive rats (SHR) were exposed to intravenous injection of 10 mg/kg LPS. Survival rate at 24 hours was markedly higher in SHR than in WKY (12 of 15 and 3 of 15, respectively ; P<0.01). Survival of LPS-injected SHR was not related to their hyper tension because hydralazine-treated SHR with normalized pressure had s imilar survival rates, and WKY made hypertensive by clipping of one re nal artery showed fatality similar to that of normotensive WKY. Contin uous arterial pressure and sequential plasma levels of interleukin-6 ( IL-6) and tumor necrosis factor (TNF) were measured in LPS-treated SHR and WKY. Both the duration of the delayed hypotensive phase and the s ystemic release of IL-6 were much lower in SHR than WKY, whereas both acute hypotension and plasma TNF peak were equivalent. We further expl ored in vitro the inflammatory response and showed that LPS-activated whole blood from SHR produced less TNF and IL-6 than WKY LPS-activated whole blood. Our results indicate that SHR have a greater ability to resist endotoxic shock than WKY. This is not related to their hyperten sion but is associated with an attenuated inflammatory response to LPS .