Renal responses to severe haemorrhage in conscious lambs: role of kappa opioid receptors (1157.1)

Abstract

In previous studies, we showed that activation of kappa opioid receptors (KORs) alters cardiorenal function in conscious newborn lambs. The endogenous ligand for KORs, Dynorphin, is increased in response to blood loss, although any role for KORs in the renal responses to haemorrhage in the newborn is not known. Therefore, in conscious newborn lambs (N=7, aged 7 to 9 days), various parameters of glomerular and tubular function were measured for 30 min before (Control) and 120 min after 30% haemorrhage after pretreatment with vehicle (experiment one) or the selective KOR antagonist, GNTI (experiment two). After vehicle, glomerular filtration rate decreased 30 min after haemorrhage from 0.24±0.08 to 0.14±0.05 mL/min/g and remained at 0.19±0.08 mL/min/g at 120 min. Renal plasma flow decreased by 30 min from 1.5±0.5 to 0.7±0.2 and then increased to 1.1±0.4 mL/min/g after 120 min. Urinary flow rates and electrolyte clearances also decreased after haemorrhage. These renal responses were not altered by pretreatment with GNTI. In contrast, after vehicle, free water clearance decreased from ‐0.6±1.8 to ‐1.8±1.2 μL/min/g 30 min after haemorrhage, but increased after pretreatment with GNTI from ‐1.1±1.0 to 1.3±0.6 μL/min/g. Therefore, in the newborn period, KORs appear to regulate tubular water reabsorption but are not involved in other tubular or glomerular responses to severe blood loss.Grant Funding Source: Supported by the CIHR.