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The new nitric oxide donor 2-nitrate-1,3-dibuthoxypropan alters autonomic function in spontaneously hypertensive rats.

Abstract
Previously, we found that the nitrate synthesized from glycerin, 2-nitrate-1,3-dibuthoxypropan (NDBP), increased NO levels in rat aortic smooth muscle cells, inducing vasorelaxation in mesenteric artery. However, its effects on blood pressure and heart rate as well as on autonomic function were not investigated. This study evaluated the action of NDBP on these cardiovascular parameters in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. We found that NDBP causes a biphasic response: hypotension and bradycardia followed by hypertension and tachycardia in WKY and SHR rats. Atropine (2mg/kg) blunted the hypotension induced by NDBP (15 mg/kg) in WKY and SHR (-75 ± 9 vs -12 ± 3 mmHg, n=6; -101 ± 6 vs -7 ± 2 bpm, n=6; respectively, p<0.05) and the pressor response to the compound was potentiated. Furthermore, vagotomy reduced the bradycardia in WKY and SHR (-136 ± 8 vs -17 ± 2, n=4, p<0.05; -141 ± 9 vs -8 ± 2, n=6, p<0.05). Moreover, hexamethonium (30 mg/kg) reduced both bradycardia (-278 ± 23 vs -48 ± 3 in WKY; -285 ± 16 vs -27 ± 19 in SHR, n=4; p<0.05) and pressor response (28 ± 8 vs -9 ± 5-WKY, n=6; 42 ± 7 vs -19 ± 8-SHR, n=5; p<0.05). In addition, administration of methylene blue (4 mg/kg) attenuated the hypotensive and bradycardic responses to the NDBP in all groups. In conclusion, NDBP induces bradycardia by direct vagal stimulation and pressor response by increasing sympathetic outflow to the periphery.
AuthorsMaria S França-Silva, Matheus M O Monteiro, Thyago M Queiroz, Alexsandro F Santos, Petrônio F Athayde-Filho, Valdir A Braga
JournalAutonomic neuroscience : basic & clinical (Auton Neurosci) Vol. 171 Issue 1-2 Pg. 28-35 (Nov 02 2012) ISSN: 1872-7484 [Electronic] Netherlands
PMID23141524 (Publication Type: Journal Article)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • 2-nitrate-1,3-dibuthoxypropan
  • Enzyme Inhibitors
  • Nitrates
  • Nitric Oxide Donors
  • Parasympatholytics
  • Atropine
  • Methylene Blue
  • Propane
Topics
  • Analysis of Variance
  • Animals
  • Atropine (pharmacology)
  • Blood Pressure (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Heart Rate (drug effects)
  • Male
  • Methylene Blue (pharmacology)
  • Nitrates (chemistry, pharmacology)
  • Nitric Oxide Donors (chemistry, pharmacology)
  • Parasympatholytics (pharmacology)
  • Propane (analogs & derivatives, chemistry, pharmacology)
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Vagotomy
  • Wakefulness

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