Increased blood pressure in rats after long-term inhibition of the neuronal isoform of nitric oxide synthase.
In the kidney, nitric oxide synthase (NOS) of the neuronal isoform (nNOS) is predominantly located in the macula densa cells. Unspecific chronic NOS inhibition in rats leads to elevated blood pressure (P(A)), associated with increased renal vascular resistance. This study was designed to examine the effect of chronic selective inhibition of nNOS with 7-nitro indazole (7-NI) on P(A), GFR, and the tubuloglomerular feedback (TGF) system. P(A) was repeatedly measured by a noninvasive tail-cuff technique for 4 wk in rats treated orally with 7-NI, and in control rats. After treatment, the animals were anesthetized and renal excretion rates, GFR, and TGF activity were determined. After 1 wk of 7-NI treatment P(A) was increased from 129+/-4 to 143 2 mmHg. GFR (1.85+/-0.1 vs. 1.97+/-0.2 ml/min in controls) was unchanged, but micropuncture studies revealed a more sensitive TGF than in controls. After 4 wk of 7-NI treatment P(A) was 152+/-4 mmHg, but no change in GFR (1.90+/-0.5 ml/min) or TGF sensitivity was detected. Acute administration of 7-NI to nontreated rats did not affect P(A), but decreased GFR (1.49+/-0.1 ml/min) and increased TGF sensitivity. In conclusion, chronic nNOS inhibition leads to increased P(A). Our results suggest that the elevated P(A) could be caused by an initially increased TGF sensitivity, leading to decreased GFR and an increased body fluid volume.
Ollerstam
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A
Department of Physiology and Neuroscience, Lund University, Sweden.
Pittner
J
J
Persson
A E
AE
Thorup
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C
D000818:Animals; D001794:Blood Pressure; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D008297:Male; D009566:Nitrates / Q000032:analysis / Q000652:urine; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000032:analysis / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014554:Urination / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D007191:Indazoles; D007527:Isoenzymes; D009566:Nitrates; D009573:Nitrites; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole