Garlic extract increases non-clipped kidney tubular natriuresis and diuresis in the 2-kidney, 1-clip rat model: Significance in hypertension

BACKGROUND: Angiotensin II (AngII) is a potent modulator of vascular tone and renal clearance function. Raw garlic aqueous extract (RGAE) inhibits angiotensin I converting enzyme (ACE) dipeptidase activity and therefore AngII generation in the 2-kidney, 1-clip rat model (2K-1Cr). OBJECTIVE: This study investigated the effect of RGAE on the non-clipped kidney clearance function and blood pressure (BP) in the 2 K-1Cr. METHOD: 2K-1Cr were anesthetized, cannulated and instrumentalized and the acute effect during the first hour post-administration of a single intravenous dose of RGAE (30mg/100gb.wt/0.3ml) was tested on: 1- The ACE dipeptidase activity estimated from a reduction in the vasopressor action of angiotensin I [(AngI, 200ng/0.2ml): the precursor of AngII] in one group (n=5); 2- The non-clipped (left) kidney (LK) clearance function in a second group (n=6). Similar protocols were carried out on two groups of normal rats (Nr: n=5+n=6). RESULTS: In the 2K-1Cr, RGAE partially, however significantly, decreased the vasopressor action of AngI. Furthermore, RGAE had no effect on systolic BP, mean BP, plasma osmolarity, LK cortical circulation or glomerular filtration rate. Alternatively, RGAE significantly increased LK urine volume, fractional excretion of water, sodium clearance and fractional excretion of sodium; while significantly decreasing heart rate and LK urine osmolarity. CONCLUSIONS: Our findings suggest that a single i.v. dose of RGAE causes ACE dipeptidase inhibition, thus reducing AngII generation and bioavailability in the 2K-1Cr. This action of RGAE enhances the non-clipped kidney clearance of sodium and water by modulating the tubular handling mechanisms.