Stimulation of NTS A1 adenosine receptors differentially resets baroreflex control of regional sympathetic outputs.
Previously we showed that pressor and differential regional sympathoexcitatory responses (adrenal > renal >/= lumbar) evoked by stimulation of A(1) adenosine receptors located in the nucleus of the solitary tract (NTS) were attenuated/abolished by baroreceptor denervation or blockade of glutamatergic transmission in the NTS, suggesting A(1) receptor-elicited inhibition of glutamatergic transmission in baroreflex pathways. Therefore we tested the hypothesis that stimulation of NTS A(1) adenosine receptors differentially inhibits/resets baroreflex responses of preganglionic adrenal (pre-ASNA), renal (RSNA), and lumbar (LSNA) sympathetic nerve activity. In urethane-chloralose-anesthetized male Sprague-Dawley rats (n = 65) we compared baroreflex-response curves (iv nitroprusside and phenylephrine) evoked before and after bilateral microinjections into the NTS of A(1) adenosine receptor agonist (N(6)-cyclopentyladenosine, CPA; 0.033-330 pmol/50 nl). CPA evoked typical dose-dependent pressor and differential sympathoexcitatory responses and similarly shifted baroreflex curves for pre-ASNA, RSNA, and LSNA toward higher mean arterial pressure (MAP) in a dose-dependent manner; the maximal shifts were 52.6 +/- 2.8, 48.0 +/- 3.6, and 56.8 +/- 6.7 mmHg for pre-ASNA, RSNA, and LSNA, respectively. These shifts were not a result of simple baroreceptor resetting because they were two to three times greater than respective increases in baseline MAP evoked by CPA. Baroreflex curves for pre-ASNA were additionally shifted upward: the maximal increases of upper and lower plateaus were 41.8 +/- 16.4% and 45.3 +/- 8.7%, respectively. Maximal gain (%/mmHg) measured before vs. after CPA increased for pre-ASNA (3.0 +/- 0.6 vs. 4.9 +/- 1.3), decreased for RSNA (4.1 +/- 0.6 vs. 2.3 +/- 0.3), and remained unaltered for LSNA (2.1 +/- 0.2 vs. 2.0 +/- 0.1). Vehicle control did not alter the baroreflex curves. We conclude that the activation of NTS A(1) adenosine receptors differentially inhibits/resets baroreflex control of regional sympathetic outputs.
Scislo
Tadeusz J
TJ
Department of Physiology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA. tscislo@med.wayne.edu
Ichinose
Tomoko K
TK
O'Leary
Donal S
DS
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D000311:Adrenal Glands / Q000187:drug effects / Q000294:innervation; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects* / Q000378:metabolism; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008160:Lumbosacral Plexus / Q000187:drug effects; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D012107:Research Design; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D058907:Adenosine A1 Receptor Agonists; D043682:Receptor, Adenosine A1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine