Neuronal NOS contributes to biphasic autoregulatory response during enhanced TGF activity.
To assess the afferent arteriolar autoregulatory response during increased activity of the tubuloglomerular feedback (TGF) mechanism and to delineate the contribution of neuronal nitric oxide synthase (nNOS) to this response, afferent arteriolar diameter responses to changes in renal perfusion pressure (RPP) were monitored in vitro using the blood-perfused rat juxtamedullary nephron preparation. At RPP of 100 mmHg, basal afferent arteriolar diameter averaged 21.1 +/- 1.4 micrometer (n = 9). The initial and sustained constrictor responses of afferent arterioles to a 60-mmHg increase in RPP averaged 14.8 +/- 1.4% and 13.3 +/- 1.3%, respectively. Acetazolamide treatment, which enhances TGF responsiveness by increasing distal nephron volume delivery, significantly decreased basal afferent arteriolar diameter by 8.2 +/- 0.5% and enhanced the initial response (25.5 +/- 2.3%) to a 60-mmHg increase in RPP but did not alter the sustained response (14.3 +/- 1.5%). In another series of experiments, nNOS inhibition with 10 microM S-methyl-L-thiocitrulline (L-SMTC) significantly decreased afferent arteriolar diameter from 20.3 +/- 1.3 to 18.3 +/- 1.1 micrometer (n = 7) and enhanced both the initial (34.4 +/- 3.5%) and sustained constrictor responses (27.6 +/- 2.9%) to a 60-mmHg increase in RPP. Treatment with acetazolamide further enhanced both initial (56.4 +/- 3.0%) and sustained responses (54.6 +/- 2.7%). Interruption of distal delivery by transection of the loops of Henle prevented the enhanced responses to increases in RPP elicited with either acetazolamide or L-SMTC. These results indicate that nNOS contributes to the counteracting resetting process of biphasic afferent arteriolar constrictor responses to increases in RPP through a TGF-dependent mechanism.
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
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D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D005246:Feedback / Q000502:physiology; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology*; D007668:Kidney / Q000098:blood supply / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D002956:Citrulline; D019001:Nitric Oxide Synthase; D013890:Thiourea; C086717:S-methylthiocitrulline; D000086:Acetazolamide; D009638:Norepinephrine