Cardiovascular effects of nitrergic system of the pedunculopon-tine tegmental nucleus in anesthetized rats

Document Type: Original Article

Authors

1 Neurogenic Inflammation Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Iran

2 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran

3 Neurocognitive Research Center, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran

Abstract

Objective(s): Nitric oxide (NO) is an important neurotransmitter in central nervous system involved in central cardiovascular regulation. The presence of NO in the pedunculopontine tegmental (PPT) nucleus has been shown, but its cardiovascular effect has not been determined. In the present study, the cardiovascular effect of NO in the PPT nucleus was evaluated.
Materials and Methods: After induction of anesthesia, a polyethylene catheter (PE-50) filled with heparinized saline inserted into the femoral artery, and the blood pressure (BP) and heart rate (HR) were continuously recorded. Animals were then placed in a stereotaxic apparatus and maximum changes of mean arterial pressure (∆MAP) and heart rate (∆HR) after microinjection of two doses of NG-nitro-L-arginine methyl ester (L-NAME, 30 and 90 nmol), L-arginine (L-Arg 10 and 50 nmol) and sodium nitroprusside (SNP, 9 and 27 nmol) into the PPT were provided and compared with control group (One-way ANOVA).
Results: Both doses of L-NAME significantly increased ∆MAP compared to control (PP<0.01, respectively). ∆HR only in higher dose (90 nmol) significantly increased compared to control (P<0.05). Two doses of L-Arg (10 and 50 nmol/150 nl) had no significant effect on ∆MAP or ∆HR. Higher dose of SNP (27 nmol) significantly decreased ∆MAP (P<0.05) and its both doses significantly decreased ∆HR compared to control (PP<0.001, respectively). Effect of higher dose on ∆HR was significantly higher than the lower dose (P<0.05).
Conclusion: Our results show an inhibitory effect of the nitrergic system of the PPT on central cardiovascular system.

Keywords


1. Reese N, Garcia-Rill E, Skinner R. The pedunculopontine nucleus—auditory input, arousal and pathophysiology. Prog Neurobiol 1995; 47:105-133.

2. Topchiy I, Waxman J, Radulovacki M, Carley DW. Functional topography of respiratory, cardiovascular and pontine-wave responses to glutamate microstimulation of the pedunculopontine tegmentum of the rat. Respir Physiol Neurobiol 2010; 173:64-70.

3. Padley JR, Kumar NN, Li Q, Nguyen TB, Pilowsky PM, Goodchild AK. Central command regulation of circulatory function mediated by descending pontine cholinergic inputs to sympathoexcitatory rostral ventrolateral medulla neurons. Circ Res 2007; 100:284-291.

4. Kubo T, Hagiwara Y, Sekiya D, Fukumori R. Midbrain central gray is involved in mediation of cholinergic inputs to the rostral ventrolateral medulla of the rat. Brain Res Bull 1999; 50:41-46.

5. Steininger TL, Rye DB, Wainer BH. Afferent projections to the cholinergic pedunculopontine tegmental nucleus and adjacent midbrain extrapyramidal area in the albino rat. I. Retrograde tracing studies. J Comp Neurol 1992; 321:515-543.

6. Yasui Y, Cechetto DF, Saper CB. Evidence for a cholinergic projection from the pedunculopontine tegmental nucleus to the rostral ventrolateral medulla in the rat. Brain Res 1990; 517:19-24.

7. Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J 2001; 357:593-615.

8. Krukoff TL. Central actions of nitric oxide in regulation of autonomic functions. Brain Res Rev 1999; 30:52-65.

9. Umans JG, Levi R. Nitric oxide in the regulation of blood flow and arterial pressure. Annu Rev Physiol 1995; 57:771-790.

10. Pechánová O, Bernátová I, Babál P, Martínez MC, Kyselá S, Stvrtina S, et al. Red wine polyphenols prevent cardiovascular alterations in L-NAME-induced hypertension. J Hypertens 2004; 22:1551-1559.

11. Khayyal MT, El-Ghazaly MA, Abdallah DM, Nassar NN, Okpanyi SN, Kreuter MH. Blood pressure lowering effect of an olive leaf extract {Olea europaed) in L-NAME induced hypertension in rats. Arzneimittelforschung 2002; 52:797-802.

12. Heesch CM, Zheng H, Foley CM, Mueller PJ, Hasser EM, Patel KP. Nitric oxide synthase activity and expression are decreased in the paraventricular nucleus of pregnant rats. Brain Res 2009; 1251:140-150.

13. Lo WC, Lin HC, Ger LP, Tung CS, Tseng CJ. Cardiovascular effects of nitric oxide and N-methyl-D-aspartate receptors in the nucleus tractus solitarii of rats. Hypertension 1997; 30:1499-1503.

14. Reddy MK, Schultz HD, Zheng H, Patel KP. Altered nitric oxide mechanism within the paraventricular nucleus contributes to the augmented carotid body chemoreflex in heart failure. Am J Physiol Heart Circ Physiol 2007; 292:H149-H157.

15. Tseng CJ, Liu HY, Lin HC, Ger LP, Tung CS, Yen MH. Cardiovascular effects of nitric oxide in the brain stem nuclei of rats. Hypertension 1996; 27:36-42.

16. Togashi H, Sakuma I, Yoshioka M, Kobayashi T, Yasuda H, Kitabatake A, et al. A central nervous system action of nitric oxide in blood pressure regulation. J Pharmacol Exp Ther 1992; 262:343-347.

17. Kagiyama S, Tsuchihashi T, Abe I, Fujishima M. Cardiovascular effects of nitric oxide in the rostral ventrolateral medulla of rats. Brain Res 1997; 757:155-158.

18. Patel KP, Li YF, Hirooka Y. Role of nitric oxide in central sympathetic outflow. Exp Biol Med 2001; 226:814-824.

19. Datta S, Patterson EH, Siwek DF. Endogenous and exogenous nitric oxide in the pedunculopontine tegmentum induces sleep. Synapse 1997; 27:69-78.

20. Paxinos GW, Watson C. The rat brain in stereotaxic coordinates. Burlington MA Elsevier Inc 2005.

21. Shafei MN, Alaei H, Farrokhi E. Effect of reversible inactivation of the Kolliker fuse nucleus on basal blood pressure and heart rate in anesthetized rat. Basic Clin Neurosci. 2011; 3:4-8.

22. Shafei MN, Nasimi A. Effect of glutamate stimulation of the cuneiform nucleus on cardiovascular regulation in anesthetized rats: Role of the pontine Kolliker–Fuse nucleus. Brain Res 2011; 1385:135-143.

23. Tai MH, Weng WT, Lo WC, Chan JY, Lin C-J, Lam HC, et al. Role of nitric oxide in α-melanocyte-stimulating hormone-induced hypotension in the nucleus tractus solitarii of the spontaneously hypertensive rats. J Pharmacol Exp Ther 2007; 321:455-461.

24. Forestiero D, Manfrim CM, Guimarães FS, de Oliveira RMW. Anxiolytic-like effects induced by nitric oxide synthase inhibitors microinjected into the medial amygdala of rats. Psychopharmacology 2006; 184:166-172.

25. Guimarães FS, de Aguiar JC, Del Bel EA, Ballejo G. Anxiolytic effect of nitric oxide synthase inhibitors microinjected into the dorsal central grey. Neuroreport 1994; 5:1929-1932.

26. Lin HC, Wan FJ, Cheng KK, Tseng CJ. Nitric oxide signaling pathway mediates the L-arginine-induced cardiovascular effects in the nucleus tractus solitarii of rats. Life Sci 1999; 65:2439-2451.

27. Busnardo C, Crestani CC, Tavares RF, Resstel LB, Correa FM. Cardiovascular responses to L-glutamate microinjection into the hypothalamic paraventricular nucleus are mediated by a local nitric oxide-guanylate cyclase mechanism. Brain Res 2010; 1344:87-95.

28. Nasimi A, Kafami M. Vasopressin and sympathetic system mediate the cardiovascular effects of the angiotensin II in the bed nucleus of the stria terminalis in rat. Neurosci Res 2016; 108:34-39.

29. Shafei MN, Niazmand S, Hosseini M, Daloee MH. Pharmacological study of cholinergic system on cardiovascular regulation in the cuneiform nucleus of rat. Neurosci Lett 2013; 549:12-17.

30. Ishide T, Amer A, Maher TJ, Ally A. Nitric oxide within periaqueductal gray modulates glutamatergic neurotransmission and cardiovascular responses during mechanical and thermal stimuli. Neurosci Res 2005; 51:93-103.

31. Morimoto S, Sasaki S, Miki S, Kawa T, Nakamura K, Itoh H, et al. Nitric oxide is an excitatory modulator in the rostral ventrolateral medulla in rats. Am J Hypertens 2000; 13:1125-1134.

32. Rossi NF, Black SM, Telemaque-Potts S, Chen H. Neuronal nitric oxide synthase activity in the paraventricular nucleus buffers central endothelin-1-induced pressor response and vasopressin secretion. J Cardiovasc Pharmacol 2004; 44:S283-S288.

33. Rossi NF, Maliszewska‐Scislo M, Chen H, Black SM, Sharma S, Ravikov R, et al. Neuronal nitric oxide synthase within paraventricular nucleus: blood pressure and baroreflex in two‐kidney, one‐clip hypertensive rats. Exp Physiol 2010; 95:845-857.

34. Zhang K, Mayhan WG, Patel KP. Nitric oxide within the paraventricular nucleus mediates changes in renal sympathetic nerve activity. Am J Physiol Regul Integr Comp Physiol 1997; 273:R864-R872.

35. Chowdhary S, Townend JN. Role of nitric oxide in the regulation of cardiovascular autonomic control. Clin Sci 1999; 97:5-17.

36. Guyenet PG. The sympathetic control of blood pressure. Nat Rev Neurosci 2006; 7:335-346.

37. Dampney R. Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 1994; 74:323-364.

38. Datta S, Spoley EE, Patterson EH. Microinjection of glutamate into the pedunculopontine tegmentum induces REM sleep and wakefulness in the rat. Am J Physiol Regul Integr Comp Physiol 2001; 280:R752-R759.

39. Spann BM, Grofova I. Cholinergic and non-cholinergic neurons in the rat pedunculopontine tegmental nucleus. Anat Embryol (Berl) 1992; 186:215-227.

40. Wang HL, Morales M. Pedunculopontine and laterodorsal tegmental nuclei contain distinct populations of cholinergic, glutamatergic and GABAergic neurons in the rat. Eur J Neurosci 2009; 29:340-358.

41. Bevan M, Bolam J. Cholinergic, GABAergic, and glutamate-enriched inputs from the mesopontine tegmentum to the subthalamic nucleus in the rat. J Neurosci 1995; 15:7105-7120.

42. Sartori C, Lepori M, Scherrer U. Interaction between
nitric oxide and the cholinergic and sympathetic nervous system in cardiovascular control in humans. Pharmacol Ther. 2005; 106:209-220.

43. Zhang K, Patel KP. Effect of nitric oxide within the paraventricular nucleus on renal sympathetic nerve discharge: role of GABA. Am J Physiol Regul Integr Comp Physiol 1998; 275:R728-R734.

44. Martins-Pinge MC, Mueller PJ, Foley CM, Heesch CM, Hasser EM. Regulation of arterial pressure by the paraventricular nucleus in conscious rats: interactions among glutamate, GABA, and nitric oxide. Front Physiol 2013; 3:490.

45. Ishide T, Hara Y, Maher TJ, Ally A. Glutamate neurotransmission and nitric oxide interaction within the ventrolateral medulla during cardiovascular responses to muscle contraction. Brain Res 2000; 874:107-115.

46. Martins-Pinge MC, Baraldi-Passy I, Lopes OU. Excitatory effects of nitric oxide within the rostral ventrolateral medulla of freely moving rats. Hypertension 1997; 30:704-707.

47. Rye DB. Contributions of the pedunculopontine region to normal and altered REM sleep. Sleep 1997; 20:757-788. Review.

48. El Mansari M, Sakai K, Jouvet M. Unitary characteristics of presumptive cholinergic tegmental neurons during the sleep-waking cycle in freely moving cats. Exp Brain Res 1989; 76:519-529.