Nitric oxide inhibition in rats improves blood pressure and renal function during hypovolemic shock.
We have examined the systemic and renal hemodynamic effects of nitric oxide (NO) inhibition with NG-monomethyl-L-arginine (L-NMMA) in normotensive rats as well as in rats with hypovolemic shock induced by hemorrhage. L-NMMA increased mean arterial blood pressure (MAP) from 114 +/- 4 to 130 +/- 6 mmHg (P less than 0.05) in the nonhemorrhaged rats and from 61 +/- 3 to 89 +/- 3 mmHg (P less than 0.05) in the hypovolemic animals. The absolute increase in MAP was greater in the hypovolemic (31 +/- 3 mmHg) than in the nonhemorrhaged (15 +/- 2 mmHg) rats (P less than 0.05). An excess of L-arginine reversed the increase in MAP induced by L-NMMA in both groups. In the normotensive rats the increase in blood pressure was associated with an elevation in renal vascular resistance (RVR; from 6.5 +/- 0.7 to 8.2 +/- 0.9 mmHg.ml-1.min-1, P less than 0.05) so that renal plasma flow (RPF) and glomerular filtration rate (GFR) were unchanged. In contrast, in the hypotensive rats, the marked increase in MAP induced by L-NMMA infusion was not associated with a significant increase in RVR. As a result L-NMMA increased both RPF (from 6.0 +/- 0.4 to 7.8 +/- 0.4 ml/min, P less than 0.05) as well as GFR (from 1.7 +/- 0.2 to 2.5 +/- 0.2 ml/min, P less than 0.05). We conclude that NO is produced and modulates peripheral resistance in normotensive rats as well as in rats with hypovolemic shock. In the hypovolemic rats NO inhibition substantially improves RPF and GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
Lieberthal
W
W
Evans Memorial Department of Clinical Research, University Hospital, Boston University Medical Center, Massachusetts 02118.
McGarry
A E
AE
Sheils
J
J
Valeri
C R
CR
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006470:Hemorrhage / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D012769:Shock / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine