Abstract 499: Renal Endocannabinoids in Salt-Sensitive Hypertension of SHR

Abstract

Recent evidence suggests that endocannabinoids (ECs) acting on two major cannabinoid receptors (CB 1 and CB 2 ) regulate blood pressure and cardiovascular and renal function in health and disease. However, there is no evidence of the role of ECs in the salt-induced renal damage in hypertensive subjects. In the present study we investigated changes in the content of two major ECs, 2-arachidonoylglycerol (2-AG) and anandamide ( N -arachidonoylethanolamine), and related functional changes in the kidneys of spontaneously hypertensive rats (SHR) in response to increased dietary salt intake. Male SHRs were given an 8% salt diet (HS; n=7), while their age-matched controls (C; n=7) received standard chow for 5 weeks. ECs were measured by UPLC/MS-MS methods on Applied Biosystems Mass Spectrometry Systems. After 5 weeks on a high salt diet, renal 2-AG (4.29 ± 0.40 vs. 3.32 ± 0.17 ng/mg; p<0.05) but not anandamide (2.12 ± 0.17 vs. 2.27 ± 0.07 pg/mg) increased in the salt-loaded SHR. Dietary salt excess increased mean arterial pressure (203 ± 5 vs. 171 ± 7 mmHg; p<0.05), urinary protein excretion (159 ± 37 vs. 22 ± 2 mg/day), and significantly decreased renal blood flow measured by flow probe (2.93 ± 0.55 vs. 6.67 ± 0.56 ml/min/mg; p<0.05) and glomerular filtration rate assessed by creatinine clearance (1.15 ± 0.14 vs. 1.77 ± 0.08 ml/min; p<0.05). Our previous study showed a reduction in CB 1 receptor mRNA while CB 2 receptor gene expression was increased in the kidney of salt-loaded SHR. Together these results suggest that alterations in renal ECs may play a significant role in the development of renal injury due to high dietary salt intake.