Reduced rat renal vascular response to angiotensin II after chronic inhibition of nNOS.
The neuronal isoform of nitric oxide synthase (nNOS) in the kidney is predominantly located in the macula densa (MD) cells. These cells are known to be the sensor in the tubuloglomerular feedback, which influences the tonus of the afferent arteriole. This study investigated the effect of angiotensin II (Ang II) after chronic inhibition of nNOS on renal blood flow (RBF) and cytosolic calcium concentration [Ca(2+)]i in smooth muscle cells from afferent arterioles. Measurements of RBF were made in two control groups and two groups treated with a nNOS inhibitor, 7-nitro indazole (7-NI), for 1 and 4 weeks. At the time of the experiment Ang II bolus was given in the renal artery before and during i.v. l-NNA. [Ca(2+)]i was measured in arterioles from control rats and from rats treated for 1 week with 7-NI. RBF decreased after bolus Ang II by 60 +/- 11% in the control vs. 23 +/- 8% in the 1 week 7-NI treated group. The decreased sensitivity to Ang II after 1 week of 7-NI treatment compared with control rats persisted after l-NNA infusion. There were no differences from control in the group treated for 4 weeks. Ang II gave a transient [Ca(2+)]i increase in vessels from control rats whereas this response was absent in 1 week 7-NI-treated rats. A possible explanation for these findings could be a down regulation of Ang II receptors. The renal vasculature of rats exhibits a diminished RBF and [Ca(2+)]i response to Ang II after 1 week blockade of nNOS.
Ollerstam
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Division of Integrative Physiology, BMC, University of Uppsala, Uppsala, Sweden.
Salomonsson
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M
Persson
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D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001783:Blood Flow Velocity / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002118:Calcium / Q000032:analysis; D003600:Cytosol / Q000378:metabolism; D007668:Kidney / Q000502:physiology; D007678:Kidney Glomerulus / Q000098:blood supply / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*
D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D002118:Calcium