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

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.