Faculty Collaboration Database

Inducible nitric oxide synthase and blood pressure. Hypertension 1998 Jan;31(1):15-20

Date

02/04/1998

Pubmed ID

9449384

DOI

10.1161/01.hyp.31.1.15

Scopus ID

2-s2.0-0031939771 (requires institutional sign-in at Scopus site)   80 Citations

Abstract

In the present studies, the influence of inducible nitric oxide synthase (NOS) inhibition with aminoguanidine on renal function and blood pressure was examined in rats. Intravenous aminoguanidine infusion (60 mg x kg-1 x hr-1) for 40 minutes to anesthetized Sprague-Dawley rats (n=7) resulted in no significant changes in mean arterial pressure or renal cortical blood flow, while medullary blood flow was slightly increased. Despite minimal effects on renal blood flow, urine flow was significantly decreased from 14.2+/-2.7 to 10.4+/-2.3 microL x min-1 x g kidney wt-1 during aminoguanidine infusion. To examine the possible effects of inducible NOS on blood pressure, aminoguanidine (10 mg x kg-1 x h-1 IV) was infused chronically into uninephrectomized rats maintained on a high salt (4.0% NaCl) diet. Mean arterial pressure significantly increased from 104+/-2 to 118+/-3 mm Hg after 6 days of aminoguanidine infusion (n=7) and returned to levels not different from those in the control group after 2 days of postcontrol infusion. Calcium-independent NOS activity in the renal medulla, a tissue that expresses inducible NOS in normal rats, was significantly decreased by 49% in the aminoguanidine-infused group (n=6) compared with that activity in the vehicle-infused control animals (n=6). In contrast, calcium-dependent NOS activity in the renal medulla was not significantly altered by aminoguanidine infusion, indicating specificity of aminoguanidine for inducible NOS in these experiments. In a final group of rats (n=5), oral L-arginine administration in drinking water (2% wt/vol) increased plasma arginine levels from 118+/-5 to 232+/-16 micromol/L and blocked the increase in arterial pressure after 6 days of aminoguanidine infusion. The present experiments provide evidence supporting a role for inducible NOS in the control of arterial pressure, possibly by renal tubular effects.

Author List

Mattson DL, Maeda CY, Bachman TD, Cowley AW Jr

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arginine
Blood Pressure
Enzyme Inhibitors
Guanidines
Infusions, Intravenous
Kidney Medulla
Male
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Rats
Rats, Sprague-Dawley
Renal Circulation
Sodium
Urine