Abstract
The involvement of the corticotropin-releasing hormone (CRH) type 1 receptor in CRH-induced cardiac responses was studied in freely moving rats. Intracerebroventricular (icv) infusion of 2 μg CRH under resting conditions resulted in a significant increase in heart rate (HR), but did not significantly affect the PQ interval of the electrocardiogram. This effect involves sympathetic nervous system (SNS) activation, since CRH-treatment resulted in a marked increase in plasma norepinephrine (NE) and epinephrine (E), and sympathetic blockade by subcutaneously injected atenolol (1 mg/kg), a β1-selective adrenergic antagonist, completely prevented the CRH-induced tachycardia. CRH infusion after sympathetic blockade resulted in an elongation of the PQ interval, indicating CRH-induced vagal activation. Gross locomotor activity (GA) was determined to study its possible indirect effects on cardiac activity. Although CRH induced a marked increase in GA, this effect followed the tachycardiac response, indicating that the HR response was not a consequence of increased locomotor activity, but was a direct effect of icv CRH. Treatment with CP-154,526 (icv, 10 or 25 μg), a selective CRH type 1 receptor antagonist, did not affect baseline HR, plasma NE and E, whereas it partially blocked the CRH-induced increase in HR, plasma NE and E levels. CP-154,526 treatment had no significant effects on baseline or CRH-induced changes in GA. These results indicate that CRH activates the sympathetic nervous system at least in part via the CRH type 1 receptor.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Brown MJ, Brown DC, Murphy MB . (1983): Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med 309(23):1414–1419
Brown MR, Fisher LA, Spiess J, Rivier C, Rivier J, Vale WW . (1982): Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism. Endocrinology 111: 928–931
Brown MR, Fisher LA . (1985): Corticotropin-releasing factor: effects on the autonomic nervous system and visceral systems. Federation Proc 44: 243–248
Chalmers DT, Lovenberg TW, De Souza EB . (1995): Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: comparison with CRF1 receptor mRNA expression. J Neurosci 15(10):6340–6350
Croiset G, Raats CJI, Nijsen MJMA, Wiegant VM . (1994): Differential effects of cholinergic and adrenergic agents on P-R and R-R intervals in rat ECG. Neurosci Res Commun 14: 75–84
Diamant M, De Wied D . (1991): Autonomic and behavioral effects of centrally administered corticotropin-releasing factor in rats. Endocrinology 129: 446–454
Dieterich KD, Lehnert H, De Souza EB . (1997): Corticotropin-releasing factor receptors: an overview. Exp Clin Endocrinol Diabetes 105(2):65–82
Fisher LA, Jessen G, Brown MR . (1983): Corticotropin-releasing factor (CRF): mechanism to elevate mean arterial pressure and heart rate. Regul Pept 5: 153–161
Fisher LA . (1989): Central autonomic modulation of cardiac baroreflex by corticotropin-releasing factor. Am J Physiol 256: H949–H955
Grigoriadis DE, Lovenberg TW, Chalmers DT, Liaw C, De Souza EB . (1996): Characterization of corticotropin-releasing factor receptor subtypes. In: Crawley JN, McLean S, editors. Annals of the New York Academy of Sciences; Neuropeptides: basic and clinical advances. 780th. New York:New York Academy of Sciences. pp 60–80.
Grosskreutz CL, Brody MJ . (1988): Regional hemodynamic responses to central administration of corticotropin-releasing factor (CRF). Brain Res 442: 363–367
Hall JA, Petch MC, Brown MJ . (1991): In vivo demonstration of cardiac beta 2-adrenoreceptor sensitization by beta 1-antagonist treatment. Circ Res 69(4):959–964
Heinrichs SC, Lapsansky J, Lovenberg TW, De Souza EB, Chalmers DT . (1997): Corticotropin-releasing factor CRF1, but not CRF2, receptors mediate anxiogenic-like behavior. Regul Pept 71(1):15–21
Korte SM, Bouws GAH, Bohus B . (1993): Central actions of corticotropin-releasing hormone (CRH) on behavioral, neuroendocrine, and cardiovascular regulation: brain corticoid receptor involvement. Hormones and Behavior 27: 167–183
Lake CR, Ziegler MG, Kopin IJ . (1976): Use of plasma norepinephrine for evaluation of sympathetic neuronal function in man. Life Sciences 18: 1315–1325
Levy MN, Zieske H . (1969): Autonomic control of cardiac pacemaker activity and atrioventricular transmission. J Appl Physiol 27: 465–470
Nijsen MJMA, Croiset G, Diamant M, Broekhoven MH, De Wied D, Wiegant VM . (1998a): Vagal activation in novelty-induced tachycardia during the light phase in the rat. Physiol Behav 63(2):233–239
Nijsen MJMA, Croiset G, Diamant M, Stam R, Delsing D, De Wied D, Wiegant VM . (1998b): Conditioned fear-induced tachycardia in the rat; vagal involvement. Eur J Pharmacol 350: 211–222
Overton JM, Davis-Gorman G, Fisher LA . (1990a): Central nervous effects of CRF and angiotensin II on cardiac output in conscious rats. J Appl Physiol 69: 788–791
Overton JM, Davis-Gorman G, Fisher LA . (1990b): Central nervous system cardiovascular actions of CRF in sinoaortic–denervated rats. Am J Physiol 258: R596–R601
Primus RJ, Yevich E, Baltazar C, Gallager DW . (1997): Autoradiographic localization of CRF1 and CRF2 binding sites in adult rat brain. Neuropsychopharmacology 17(5):308–316
Schulz DW, Mansbach RS, Sprouse J, Braselton JP, Collins J, Corman M, Dunaiskis A, Faraci S, Schmidt AW, Seeger T, Tingley FD, Winston E, Chen YL, Heym J . (1996): CP-154,526, a potent and selective nonpeptide antagonist of corticotropin releasing factor receptors. Proc Natl Acad Sci U S A 93: 10477–10482.
Smith GW, Aubry JM, Dellu F, Contarino A, Bilezikjian LM, Gold LH, Chen R, Marchuk Y, Hauser C, Bentley CA, Sawchenko PE, Koob GF, Vale W, Lee KF . (1998): Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development. Neuron 20(6):1093–1102
Steffens AB . (1969): A method for frequent sampling of blood and continuous infusion of fluids in the rat without disturbing the animal. Physiol Behav 4: 833–836
Takei M, Furukawa Y, Narita M, Murakami M, Ren LM, Karasawa Y, Chiba S . (1992): Sympathetic stimulation activates both beta 1- and beta 2-adrenoceptors of SA and AV nodes in anesthetized dog hearts. Jpn J Pharmacol 59(1):23–30
Timpl P, Spanagel R, Sillaber I, Kresse A, Reul JM, Stalla GK, Blanquet V, Steckler T, Holsboer F, Wurst W . (1998): Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor. Nat Genet 19(2):162–166
Van Oers JWAM, Tilders FJH . (1991): Non-adrenocorticotropin mediated effects of endogenous corticotropin-releasing factor on the adrenocortical activity in the rat. J Neuroendocrinol 3: 119–121
Acknowledgements
The authors thank M.H. Broekhoven, M. Agterberg, J.C. Frankhuijzen and H.A. Spierenburg for their skilled technical assistance.
This research is supported by a research grant from the Netherlands Heart Foundation.
R. Stam was supported by the Janssen Research Foundation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nijsen, M., Croiset, G., Stam, R. et al. The Role of the CRH Type 1 Receptor in Autonomic Responses to Corticotropin-Releasing Hormone in the Rat. Neuropsychopharmacol 22, 388–399 (2000). https://doi.org/10.1016/S0893-133X(99)00126-8
Received:
Revised:
Accepted:
Issue date:
DOI: https://doi.org/10.1016/S0893-133X(99)00126-8
Keywords
This article is cited by
-
Methamphetamine withdrawal induces activation of CRF neurons in the brain stress system in parallel with an increased activity of cardiac sympathetic pathways
Naunyn-Schmiedeberg's Archives of Pharmacology (2018)
-
ACTH and cortisol responses to CRH in acute, subacute, and prolonged critical illness: a randomized, double-blind, placebo-controlled, crossover cohort study
Intensive Care Medicine (2018)
-
Ganglionic blockade alters behavioral and cerebral metabolic responses to corticotropin releasing factor in the rat
Journal of Neural Transmission (2013)
-
Depressive and cardiovascular disease comorbidity in a rat model of social stress: a putative role for corticotropin-releasing factor
Psychopharmacology (2012)
-
Organization of brain somatomotor-sympathetic circuits
Experimental Brain Research (2008)
