Experimental physiology
-
Experimental physiology · Nov 2012
ReviewNovel targets for sepsis-induced kidney injury: the glomerular arterioles and the sympathetic nervous system.
Sepsis and septic shock are the most common causes of acute kidney injury (AKI) in the intensive care unit, and mortality remains high despite improvements in our ability to support vital organs. The lack of development of effective treatments is partly because there has been little advance in our understanding of the pathophysiology of septic AKI, owing to the difficulty in conducting experiments on critically ill patients and use of inappropriate experimental models. Recently, however, a number of new concepts have emerged that challenge existing dogma and give insights into the causes of AKI. ⋯ New evidence also indicates that the increased sympathetic nerve activity that occurs in sepsis may contribute to the induction of organ failure. Experimental studies indicate that inhibition of central sympathetic outflow with α(2)-adrenoceptor agonists or treatment with β(1)-adrenoceptor antagonists might reduce mortality in experimental endotoxaemia and sepsis. The possibility that these beneficial actions are partly dependent on a reduction in the excessive cytokine release caused by marked and prolonged sympathetic activation is discussed.
-
Experimental physiology · Nov 2012
Increased central and peripheral inflammation and inflammatory hyperalgesia in Zucker rat model of leptin receptor deficiency and genetic obesity.
This study investigated whether sensitivity to nociceptive stimuli is altered in obese rats using established models of inflammatory pain, and using real-time PCR, profiled alterations in expression of key adipokine and inflammatory mediator mRNA (adiponectin, tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, inducible nitric oxide synthase (iNOS)) in spinal cord with obesity. Responses to thermal and mechanical stimulation of the hindpaw and paw oedema were assessed in adult male Zucker fatty rats (fa/fa) and their lean littermates (fa/-; n = 6-9 per group) in the absence of inflammation (acute nociception), then in response to intradermal hindpaw injection of carrageenan (3%; 50 μl) or capsaicin (10 μg; 50 μl) or hindpaw incision. The analgesic potency of morphine (1, 2.5 or 5 mg kg(-1) or vehicle; s.c.) was also assessed. ⋯ No difference in the capsaicin- or paw-incision-induced pain sensitivity or in the analgesic potency of morphine was observed between groups. Levels of adiponectin and inducible nitric oxide synthase mRNA were downregulated in spinal cord from obese rats, whereas tumour necrosis factor-α mRNA was upregulated; interleukin-1β and cyclo-oxygenase were unchanged. The increased pain sensitivity and inflammatory response together with changes in spinal adipokine expression in obese rats fit well with the hypothesis that obesity is a chronic low-grade inflammatory disorder, producing a state where responses to subsequent inflammatory challenge are potentiated.