Effect of reduction of nitric oxide on plasma and kidney tissue angiotensin II levels.
Nitric oxide synthase (NOS) blockade increases blood pressure (BP) and modifies glomerular and tubular function. Angiotensin II (AII) blockade restores glomerular and tubular function but does not lower BP. We measured plasma renin activity (PRA), plasma (AIIp), and kidney tissue (AIIk) AII with radioimmunoassay to investigate the dissociation between renal and systemic effects of NOS blockade. Two period clearance studies followed by plasma and renal tissue harvesting were performed in seven groups of rats. Groups 1 and 1A served as controls. Groups 2 and 2A received NaCl-NaHCO3 during the first period and N(G)-monomethyl-L-arginine (L-NMMA, 0.5 mg/kg/min) during the second period. Group 3 was similar to group 2 but renal perfusion pressure (RPP) was maintained constant by using an aortic snare. Groups 4 and 4A received N(G)-nitro-L-arginine-methyl ester (L-NAME, 5 mg/100 mL of drinking water) for 2 weeks. NOS blockers decreased AIIp (group 1, 74 +/- 7 pg/mL; group 2, 22 +/- 1 pg/mL; group 3, 26 +/- 1 pg/mL; group 4, 19 +/- 3 pg/mL). The decrease in AIIp was a direct effect of L-NMMA independent of changes in perfusion pressure, as AIIp was similar in group 3 (normal RPP) and groups 2 and 4 (increased RPP). Measurements of PRA and AIIp demonstrated a similar reduction in PRA and AIIp in rats treated with NOS blocker. Although NOS blockers decreased AIIp, acute or chronic administration of NOS blockers did not modify AIIk (group 1, 1,192 +/- 51; group 2, 1,354 +/- 85; group 3, 1,348 +/- 180; group 4, 1,276 +/- 172 pg/kidney). Our findings demonstrate that NO blockers produce a dissociation between plasma and kidney AII levels. This dissociation can explain the beneficial effects of AII blockers on renal function and their lack of antihypertensive effects in anesthetized rats treated with NOS blockers.
Garcia
G E
GE
Division of Nephrology-Hypertension, Veterans Affairs Medical Center and University of California, San Diego School of Medicine, La Jolla 92161, USA.
Brown
M R
MR
Wead
L M
LM
Braun
S
S
Gabbai
F B
FB
D000804:Angiotensin II / Q000032:analysis* / Q000097:blood; D000818:Animals; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000737:chemistry*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012083:Renin