Impaired renal haemodynamic response to L-arginine in essential hypertension: role of buffering anion and tubuloglomerular feedback.
OBJECTIVE
To investigate whether changes in tubuloglomerular feedback (TGF) dependent upon the tubular effects of buffering anions affect the renal haemodynamic response to L-arginine in healthy (control) individuals and patients with essential hypertension.


METHODS
Mean arterial pressure (MAP), glomerular filtration rate (GFR), renal blood flow (RBF) and fractional excretion of sodium (FENa), chloride (FECl) and lithium (FELi) were measured in 10 control individuals and 10 hypertensive patients during two 3-h infusions of 0.012 mmol/kg per min L-arginine buffered with either HCl or citric acid.


RESULTS
FELi, FECl and FENa increased (P < 0.001) comparably in controls and hypertensive individuals with arginine-HCl and decreased with arginine-citrate (P < 0.001). MAP was unchanged in controls with arginine-HCl and decreased by 3% with arginine-citrate (P < 0.001), and decreased in hypertensive individuals with both arginine-HCl and arginine-citrate (by 3 and 7%, respectively; P < 0.001). GFR increased with arginine-citrate in controls and hypertensive individuals (by 6.1 and 5.4%, respectively; P < 0.001), but did not change with arginine-HCl in controls and declined by 4.6% in hypertensive individuals (P < 0.05). RBF increased equally after arginine-citrate in controls and hypertensive individuals (by 34 and 33%, respectively; P < 0.001); it also increased after arginine-HCl (22 and 13%, respectively; P < 0.001), but less than after arginine-citrate (P < 0.001), and 41% less in hypertensive individuals than in controls (P < 0.001).


CONCLUSIONS
Because arginine-HCl, unlike arginine-citrate, inhibits tubular reabsorption and elicits much less renal vasodilatation than does arginine-citrate, renal haemodynamics in response to L-arginine are modulated by changes in reabsorption and TGF according to the tubular effects of the attendant anion. As renal vasodilatation in hypertensive individuals was reduced only with arginine-HCl, which activates TGF, the blunted vasodilatation of the hypertensive kidney in response to arginine-HCl reflects an exaggerated response to an activated TGF.
Biggi
Almerina
A
Department of Clinical Sciences, University of Parma, Parma, Italy.
Carra
Nicoletta
N
Cabassi
Aderville
A
Barilli
Angela Luciana
AL
Musiari
Luisa
L
Iori
Matteo
M
De Iaco
Giuseppe
G
Azzarone
Matteo
M
Novarini
Almerico
A
Montanari
Alberto
A
D000328:Adult; D000838:Anions; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D019343:Citric Acid; D025461:Feedback, Physiological; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D006851:Hydrochloric Acid; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D014664:Vasodilation / Q000187:drug effects
D000838:Anions; D019343:Citric Acid; D001120:Arginine; D006851:Hydrochloric Acid