We hypothesized that sympathetic hyperactivity and parasympathetic insuficiency in spontaneously hypertensive rats (SHR) underlie their exaggerated cardiovascular response to acute stress and impaired adaptation to repeated restraint stress exposure compared to Wistar-Kyoto rats (WKY). Cardiovascular responses to single (120 min) or repeated (daily 120 min for 1 week) restraint were measured by radiotelemetry and autonomic balance was evaluated by power spectral analysis of systolic blood pressure variability (SBPV) and heart rate variability (HRV). Baroreflex sensitivity (BRS) was measured by the pharmacological Oxford technique. Stress-induced pressor response and vascular sympathetic activity (low-frequency component of SBPV) were enhanced in SHR subjected to single restraint compared to WKY, whereas stress-induced tachycardia was similar in both strains. SHR exhibited attenuated cardiac parasympathetic activity (high-frequency component of HRV) and blunted BRS compared to WKY. Repeated restraint did not affect the stress-induced increase in blood pressure. However, cardiovascular response during the post-stress recovery period of the 7th restraint was reduced in both strains. The repeatedly restrained SHR showed lower basal heart rate during the dark (active) phase and slightly decreased basal blood pressure during the light phase compared to stress-naive SHR. SHR subjected to repeated restraint also exhibited attenuated stress-induced tachycardia, augmented cardiac parasympathetic activity, attenuated vascular sympathetic activity and improved BRS during the last seventh restraint compared to single-stressed SHR. Thus, SHR exhibited enhanced cardiovascular and sympathetic responsiveness to novel stressor exposure (single restraint) compared to WKY. Unexpectedly, the adaptation of cardiovascular and autonomic responses to repeated restraint was more effective in SHR.

Institute of Physiology Czech Academy of Sciences Prague Czechia

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Ulrich-Lai YM, Herman JP. Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci. 2009;10:397–409. 10.1038/nrn2647. 10.1038/nrn2647 PubMed DOI PMC

McEwen BS. Stress, adaptation, and disease. Allostasis and allostatic load. Ann N Y Acad Sci. 1998;840:33–44. 10.1111/j.1749-6632.1998.tb09546.x. 10.1111/j.1749-6632.1998.tb09546.x PubMed DOI

Herman JP. Neural control of chronic stress adaptation. Front Behav Neurosci. 2013;7:61 10.3389/fnbeh.2013.00061. 10.3389/fnbeh.2013.00061 PubMed DOI PMC

Kvetnansky R, McCarty R, Thoa NB, Lake CR, Kopin IJ. Sympatho-adrenal responses of spontaneously hypertensive rats to immobilization stress. Am J Physiol. 1979;236:H457–62. 10.1152/ajpheart.1979.236.3.H457. 10.1152/ajpheart.1979.236.3.H457 PubMed DOI

Crestani CC. emotional stress and cardiovascular complications in animal models: a review of the influence of stress type. Front Physiol. 2016;7:251. 10.3389/fphys.2016.00251. 10.3389/fphys.2016.00251 PubMed DOI PMC

Paton JF, Boscan P, Pickering AE, Nalivaiko E. The yin and yang of cardiac autonomic control: vago-sympathetic interactions revisited. Brain Res. Brain Res Rev. 2005;49:555–65. 10.1016/j.brainresrev.2005.02.005. 10.1016/j.brainresrev.2005.02.005 PubMed DOI

Dos Reis DG, Fortaleza EA, Tavares RF, Corrêa FM. Role of the autonomic nervous system and baroreflex in stress-evoked cardiovascular responses in rats. Stress. 2014;17:362–72. 10.3109/10253890.2014.930429. 10.3109/10253890.2014.930429 PubMed DOI

Baudrie V, Tulen JH, Blanc J, Elghozi JL. Autonomic components of the cardiovascular responses to an acoustic startle stimulus in rats. J Auton Pharm. 1997;17:303–9. 10.1046/j.1365-2680.1997.00465.x.10.1046/j.1365-2680.1997.00465.x PubMed DOI

Casto R, Printz MP. Exaggerated response to alerting stimuli in spontaneously hypertensive rats. Hypertension. 1990;16:290–300. 10.1161/01.hyp.16.3.290. 10.1161/01.hyp.16.3.290 PubMed DOI

van den Buuse M, Wegener N. Involvement of serotonin1A receptors in cardiovascular responses to stress: a radio-telemetry study in four rat strains. Eur J Pharm. 2005;507:187–98. 10.1016/j.ejphar.2004.11.048.10.1016/j.ejphar.2004.11.048 PubMed DOI

Vodička M, Vavřínová A, Mikulecká A, Zicha J, Behuliak M. Hyper-reactivity of HPA axis in Fischer 344 rats is associated with impaired cardiovascular and behavioral adaptation to repeated restraint stress. Stress. 2020;23:667–77. 10.1080/10253890.2020.1777971. 10.1080/10253890.2020.1777971 PubMed DOI

Armario A, Gavaldà A, Martí J. Comparison of the behavioural and endocrine response to forced swimming stress in five inbred strains of rats. Psychoneuroendocrinology. 1995;20:879–90. 10.1016/0306-4530(95)00018-6. 10.1016/0306-4530(95)00018-6 PubMed DOI

Ramos A, Berton O, Mormède P, Chaouloff F. A multiple-test study of anxiety-related behaviours in six inbred rat strains. Behav Brain Res. 1997;85:57–69. 10.1016/s0166-4328(96)00164-7. 10.1016/s0166-4328(96)00164-7 PubMed DOI

Makino M, Hayashi H, Takezawa H, Hirai M, Saito H, Ebihara S. Circadian rhythms of cardiovascular functions are modulated by the baroreflex and the autonomic nervous system in the rat. Circulation. 1997;96:1667–74. 10.1161/01.cir.96.5.1667. 10.1161/01.cir.96.5.1667 PubMed DOI

Carnevali L, Sgoifo A. Vagal modulation of resting heart rate in rats: the role of stress, psychosocial factors, and physical exercise. Front Physiol. 2014;5:118. 10.3389/fphys.2014.00118. 10.3389/fphys.2014.00118 PubMed DOI PMC

Mezzacappa ES, Kelsey RM, Katkin ES, Sloan RP. Vagal rebound and recovery from psychological stress. Psychosom Med. 2001;63:650–7. 10.1097/00006842-200107000-00018. 10.1097/00006842-200107000-00018 PubMed DOI

Judy WV, Farrell SK. Arterial baroreceptor reflex control of sympathetic nerve activity in the spontaneously hypertensive rat. Hypertension. 1979;1:605–14. 10.1161/01.hyp.1.6.605. 10.1161/01.hyp.1.6.605 PubMed DOI

Sato MA, Colombari E, Morrison SF. Inhibition of neurons in commissural nucleus of solitary tract reduces sympathetic nerve activity in SHR. Am J Physiol Heart Circ Physiol. 2002;282:H1679–84. 10.1152/ajpheart.00619.2001. 10.1152/ajpheart.00619.2001 PubMed DOI

Head GA, Adams MA. Characterization of the baroreceptor heart rate reflex during development in spontaneously hypertensive rats. Clin Exp Pharm Physiol. 1992;19:587–97. 10.1111/j.1440-1681.1992.tb00509.x.10.1111/j.1440-1681.1992.tb00509.x PubMed DOI

Bencze M, Boroš A, Behuliak M, Vavřínová A, Vaněčková I, Zicha J. Changes in cardiovascular autonomic control induced by chronic inhibition of acetylcholinesterase during pyridostigmine or donepezil treatment of spontaneously hypertensive rats. Eur J Pharm. 2024;971:176526 10.1016/j.ejphar.2024.176526.10.1016/j.ejphar.2024.176526 PubMed DOI

Janssen BJ, Tyssen CM, Struyker-Boudier HA. Modification of circadian blood pressure and heart rate variability by five different antihypertensive agents in spontaneously hypertensive rats. J Cardiovasc Pharm. 1991;17:494–503. 10.1097/00005344-199103000-00020.10.1097/00005344-199103000-00020 PubMed DOI

van den Buuse M. Circadian rhythms of blood pressure, heart rate, and locomotor activity in spontaneously hypertensive rats as measured with radio-telemetry. Physiol Behav. 1994;55:783–7. 10.1016/0031-9384(94)90060-4. 10.1016/0031-9384(94)90060-4 PubMed DOI

El-Mas MM, Abdel-Rahman AA. Longitudinal studies on the effect of hypertension on circadian hemodynamic and autonomic rhythms in telemetered rats. Life Sci. 2005;76:901–15. 10.1016/j.lfs.2004.10.002. 10.1016/j.lfs.2004.10.002 PubMed DOI

Lawler JE, Cox RH, Hubbard JW, Mitchell VP, Barker GF, Trainor WP, et al. Blood pressure and heart rate responses to environmental stress in the spontaneously hypertensive rat. Physiol Behav. 1985;34:973–6. 10.1016/0031-9384(85)90022-8. 10.1016/0031-9384(85)90022-8 PubMed DOI

McDougall SJ, Lawrence AJ, Widdop RE. Differential cardiovascular responses to stressors in hypertensive and normotensive rats. Exp Physiol. 2005;90:141–50. 10.1113/expphysiol.2004.028308. 10.1113/expphysiol.2004.028308 PubMed DOI

McDougall SJ, Paull JR, Widdop RE, Lawrence AJ. Restraint stress: differential cardiovascular responses in Wistar-Kyoto and spontaneously hypertensive rats. Hypertension. 2000;35:126–9. 10.1161/01.hyp.35.1.126. 10.1161/01.hyp.35.1.126 PubMed DOI

Aoki K. Experimental studies in the relationship between endocrine organs and hypertension in spontaneously hypertensive rats. I. Effects of hypophysectomy, adrenalectomy, thyroidectomy, nephrectomy and sympathectomy on blood pressure. Jpn Heart J. 1963;4:443–61. 10.1536/ihj.4.443. 10.1536/ihj.4.443 PubMed DOI

Djordjevic J, Vuckovic T, Jasnic N, Cvijic G. Effect of various stressors on the blood ACTH and corticosterone concentration in normotensive Wistar and spontaneously hypertensive Wistar-Kyoto rats. Gen Comp Endocrinol. 2007;153:217–20. 10.1016/j.ygcen.2007.02.004. 10.1016/j.ygcen.2007.02.004 PubMed DOI

Bencze M, Vavřínová A, Zicha J, Behuliak M. Pharmacological suppression of endogenous glucocorticoid synthesis attenuated blood pressure and heart rate response to acute restraint in Wistar rats. Physiol Res. 2020;69:415–26. 10.33549/physiolres.934432. 10.33549/physiolres.934432 PubMed DOI PMC

Bechtold AG, Scheuer DA. Glucocorticoids act in the dorsal hindbrain to modulate baroreflex control of heart rate. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1003–11. 10.1152/ajpregu.00345.2005. 10.1152/ajpregu.00345.2005 PubMed DOI PMC

Scheuer DA, Bechtold AG, Vernon KA. Chronic activation of dorsal hindbrain corticosteroid receptors augments the arterial pressure response to acute stress. Hypertension. 2007;49:127–33. 10.1161/01.HYP.0000250088.15021.c2. 10.1161/01.HYP.0000250088.15021.c2 PubMed DOI PMC

Costello RE, Yimer BB, Roads P, Jani M, Dixon WG. Glucocorticoid use is associated with an increased risk of hypertension. Rheumatol (Oxf). 2021;60:132–9. 10.1093/rheumatology/keaa209.10.1093/rheumatology/keaa209 PubMed DOI PMC

Mebrahtu TF, Morgan AW, West RM, Stewart PM, Pujades-Rodriguez M. Oral glucocorticoids and incidence of hypertension in people with chronic inflammatory diseases: a population-based cohort study. CMAJ. 2020;192:E295–301. 10.1503/cmaj.191012. 10.1503/cmaj.191012 PubMed DOI PMC

Behuliak M, Bencze M, Polgárová K, Kuneš J, Vaněčková I, Zicha J. Hemodynamic response to gabapentin in conscious spontaneously hypertensive rats. Hypertension. 2018;72:676–85. 10.1161/HYPERTENSIONAHA.118.09909. 10.1161/HYPERTENSIONAHA.118.09909 PubMed DOI

Vavřínová A, Behuliak M, Bencze M, Vodička M, Ergang P, Vaněčková I, et al. Sympathectomy-induced blood pressure reduction in adult normotensive and hypertensive rats is counteracted by enhanced cardiovascular sensitivity to vasoconstrictors. Hypertens Res. 2019;42:1872–82. 10.1038/s41440-019-0319-2. 10.1038/s41440-019-0319-2 PubMed DOI

Shaffer F, Ginsberg JP. An overview of heart rate variability metrics and norms. Front Public Health. 2017;5:258. 10.3389/fpubh.2017.00258. 10.3389/fpubh.2017.00258 PubMed DOI PMC

Stauss HM. Identification of blood pressure control mechanisms by power spectral analysis. Clin Exp Pharm Physiol. 2007;34:362–8. 10.1111/j.1440-1681.2007.04588.x.10.1111/j.1440-1681.2007.04588.x PubMed DOI

Yoshimoto T, Eguchi K, Sakurai H, Ohmichi Y, Hashimoto T, Ohmichi M, et al. Frequency components of systolic blood pressure variability reflect vasomotor and cardiac sympathetic functions in conscious rats. J Physiol Sci. 2011;61:373–83. 10.1007/s12576-011-0158-7. 10.1007/s12576-011-0158-7 PubMed DOI PMC

Chapleau MW, Sabharwal R. Methods of assessing vagus nerve activity and reflexes. Heart Fail Rev. 2011;16:109–27. 10.1007/s10741-010-9174-6. 10.1007/s10741-010-9174-6 PubMed DOI PMC

Bertinieri G, di Rienzo M, Cavallazzi A, Ferrari AU, Pedotti A, Mancia G. A new approach to analysis of the arterial baroreflex. J Hypertens Suppl. 1985;3:S79–81. PubMed

Oosting J, Struijker-Boudier HA, Janssen BJ. Validation of a continuous baroreceptor reflex sensitivity index calculated from spontaneous fluctuations of blood pressure and pulse interval in rats. J Hypertens. 1997;15:391–9. 10.1097/00004872-199715040-00010. 10.1097/00004872-199715040-00010 PubMed DOI

Wu XY, Hu YT, Guo L, Lu J, Zhu QB, Yu E, et al. Effect of pentobarbital and isoflurane on acute stress response in rat. Physiol Behav. 2015;145:118–21. 10.1016/j.physbeh.2015.04.003. 10.1016/j.physbeh.2015.04.003 PubMed DOI

Morrison SF, Nakamura K, Madden CJ. Central control of thermogenesis in mammals. Exp Physiol. 2008;93:773–97. 10.1007/s10571-021-01090-7. 10.1007/s10571-021-01090-7 PubMed DOI PMC

Benini R, Oliveira LA, Gomes-de-Souza L, Crestani CC. Habituation of the cardiovascular responses to restraint stress in male rats: influence of length, frequency and number of aversive sessions. Stress. 2019;22:151–61. 10.1080/10253890.2018.1532992. 10.1080/10253890.2018.1532992 PubMed DOI

Morley RM, Conn CA, Kluger MJ, Vander AJ. Temperature regulation in biotelemetered spontaneously hypertensive rats. Am J Physiol. 1990;258:R1064–9. 10.1152/ajpregu.1990.258.4.R1064. 10.1152/ajpregu.1990.258.4.R1064 PubMed DOI

Santos CE, Benini R, Crestani CC. Spontaneous recovery, time course, and circadian influence on habituation of the cardiovascular responses to repeated restraint stress in rats. Pflug Arch. 2020;472:1495–506. 10.1007/s00424-020-02451-910.1007/s00424-020-02451-9 PubMed DOI

Yagil Y, Krakoff LR. The differential effect of aldosterone and dexamethasone on pressor responses in adrenalectomized rats. Hypertension. 1988;11:174–8. 10.1161/01.hyp.11.2.174. 10.1161/01.hyp.11.2.174 PubMed DOI

Rabasa C, Gagliano H, Pastor-Ciurana J, Fuentes S, Belda X, Nadal R, et al. Adaptation of the hypothalamus-pituitary-adrenal axis to daily repeated stress does not follow the rules of habituation: A new perspective. Neurosci Biobehav Rev. 2015;56:35–49. 10.1016/j.neubiorev.2015.06.013. 10.1016/j.neubiorev.2015.06.013 PubMed DOI

Smith TL, Hutchins PM. Central hemodynamics in the developmental stage of spontaneous hypertension in the unanesthetized rat. Hypertension. 1979;1:508–17. 10.1161/01.hyp.1.5.508. 10.1161/01.hyp.1.5.508 PubMed DOI

Dickhout JG, Lee RM. Blood pressure and heart rate development in young spontaneously hypertensive rats. Am J Physiol. 1998;274:H794–800. 10.1152/ajpheart.1998.274.3.H794. 10.1152/ajpheart.1998.274.3.H794 PubMed DOI

Itter G, Jung W, Schoelkens BA, Linz W. The isolated working heart model in infarcted rat hearts. Lab Anim. 2005;39:178–93. 10.1258/0023677053739738. 10.1258/0023677053739738 PubMed DOI

Rodrigues JQD, Camara H, da Silva Junior ED, Godinho RO, Jurkiewicz A. Intrinsic adaptation of SHR right atrium reduces heart rate. J Cardiovasc Pharm. 2019;74:542–8. 10.1097/FJC.0000000000000746.10.1097/FJC.0000000000000746 PubMed DOI

Carnevali L, Bondarenko E, Sgoifo A, Walker FR, Head GA, Lukoshkova EV, et al. Metyrapone and fluoxetine suppress enduring behavioral but not cardiac effects of subchronic stress in rats. Am J Physiol Regul Integr Comp Physiol. 2011;301:R1123–31. 10.1152/ajpregu.00273.2011. 10.1152/ajpregu.00273.2011 PubMed DOI

Trombini M, Hulshof HJ, Graiani G, Carnevali L, Meerlo P, Quaini F, et al. Early maternal separation has mild effects on cardiac autonomic balance and heart structure in adult male rats. Stress. 2012;15:457–70. 10.3109/10253890.2011.639414. 10.3109/10253890.2011.639414 PubMed DOI

Darlington DN, Kaship K, Keil LC, Dallman MF. Vascular responsiveness in adrenalectomized rats with corticosterone replacement. Am J Physiol. 1989;256:H1274–81. 10.1152/ajpheart.1989.256.5.H1274. 10.1152/ajpheart.1989.256.5.H1274 PubMed DOI

Struyker-Boudier HA, Evenwel RT, Smits JF, Van Essen H. Baroreflex sensitivity during the development of spontaneous hypertension in rats. Clin Sci (Lond). 1982;62:589–94. 10.1042/cs0620589. 10.1042/cs0620589 PubMed DOI

Sterley TL, Howells FM, Russell VA. Effects of early life trauma are dependent on genetic predisposition: a rat study. Behav Brain Funct. 2011;7:11 10.1186/1744-9081-7-11 10.1186/1744-9081-7-11 PubMed DOI PMC

Hashimoto K, Makino S, Hirasawa R, Takao T, Sugawara M, Murakami K, et al. Abnormalities in the hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats during development of hypertension. Endocrinology. 1989;125:1161–7. 10.1210/endo-125-3-1161. 10.1210/endo-125-3-1161 PubMed DOI

Morilak DA, Barrera G, Echevarria DJ, Garcia AS, Hernandez A, Ma S, et al. Role of brain norepinephrine in the behavioral response to stress. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29:1214–24. 10.1016/j.pnpbp.2005.08.007. 10.1016/j.pnpbp.2005.08.007 PubMed DOI

Willner P, Gruca P, Lason M, Tota-Glowczyk K, Litwa E, Niemczyk M, et al. Validation of chronic mild stress in the Wistar-Kyoto rat as an animal model of treatment-resistant depression. Behav Pharm. 2019;30:239–50. 10.1097/FBP.0000000000000431.10.1097/FBP.0000000000000431 PubMed DOI

De La Garza R, Mahoney JJ. A distinct neurochemical profile in WKY rats at baseline and in response to acute stress: implications for animal models of anxiety and depression. Brain Res. 2004;1021:209–18. 10.1016/j.brainres.2004.06.052. 10.1016/j.brainres.2004.06.052 PubMed DOI

Paré WP. The performance of WKY rats on three tests of emotional behavior. Physiol Behav. 1992;51:1051–6. 10.1016/0031-9384(92)90091-f. 10.1016/0031-9384(92)90091-f PubMed DOI

Sagvolden T. Behavioral validation of the spontaneously hypertensive rat (SHR) as an animal model of attention-deficit/hyperactivity disorder (AD/HD). Neurosci Biobehav Rev. 2000;24:31–9. 10.1016/s0149-7634(99)00058-5. 10.1016/s0149-7634(99)00058-5 PubMed DOI

Russell VA. Dopamine hypofunction possibly results from a defect in glutamate-stimulated release of dopamine in the nucleus accumbens shell of a rat model for attention deficit hyperactivity disorder -the spontaneously hypertensive rat. Neurosci Biobehav Rev. 2003;27:671–82. 10.1016/j.neubiorev.2003.08.010. 10.1016/j.neubiorev.2003.08.010 PubMed DOI

Sagvolden T, Johansen EB, Wøien G, Walaas SI, Storm-Mathisen J, Bergersen LH, et al. The spontaneously hypertensive rat model of ADHD - the importance of selecting the appropriate reference strain. Neuropharmacology. 2009;57:619–26. 10.1016/j.neuropharm.2009.08.004. 10.1016/j.neuropharm.2009.08.004 PubMed DOI PMC

López-Rubalcava C, Lucki I. Strain differences in the behavioral effects of antidepressant drugs in the rat forced swimming test. Neuropsychopharmacology. 2000;22:191–9. 10.1016/S0893-133X(99)00100-1. 10.1016/S0893-133X(99)00100-1 PubMed DOI

Nam H, Clinton SM, Jackson NL, Kerman IA. Learned helplessness and social avoidance in the Wistar-Kyoto rat. Front Behav Neurosci. 2014;8:109. 10.3389/fnbeh.2014.00109. 10.3389/fnbeh.2014.00109 PubMed DOI PMC

Burke NN, Coppinger J, Deaver DR, Roche M, Finn DP, Kelly J. Sex differences and similarities in depressive- and anxiety-like behaviour in the Wistar-Kyoto rat. Physiol Behav. 2016;167:28–34. 10.1016/j.physbeh.2016.08.031. 10.1016/j.physbeh.2016.08.031 PubMed DOI

Gómez F, Lahmame A, de Kloet ER, Armario A. Hypothalamic-pituitary-adrenal response to chronic stress in five inbred rat strains: differential responses are mainly located at the adrenocortical level. Neuroendocrinology. 1996;63:327–37. 10.1159/000126973. 10.1159/000126973 PubMed DOI

Marti J, Armario A. Forced swimming behavior is not related to the corticosterone levels achieved in the test: a study with four inbred rat strains. Physiol Behav. 1996;59:369–73. 10.1016/0031-9384(95)02104-3. 10.1016/0031-9384(95)02104-3 PubMed DOI

Paré WP, Redei E. Depressive behavior and stress ulcer in Wistar Kyoto rats. J Physiol Paris. 1993;87:229–38. 10.1016/0928-4257(93)90010-q. 10.1016/0928-4257(93)90010-q PubMed DOI

Pardon MC, Gould GG, Garcia A, et al. Stress reactivity of the brain noradrenergic system in three rat strains differing in their neuroendocrine and behavioral responses to stress: implications for susceptibility to stress-related neuropsychiatric disorders. Neuroscience. 2002;115:229–42. 10.1016/s0306-4522(02)00364-0. 10.1016/s0306-4522(02)00364-0 PubMed DOI

Rittenhouse PA, López-Rubalcava C, Stanwood GD, Lucki I. Amplified behavioral and endocrine responses to forced swim stress in the Wistar-Kyoto rat. Psychoneuroendocrinology. 2002;27:303–18. 10.1016/s0306-4530(01)00052-x. 10.1016/s0306-4530(01)00052-x PubMed DOI

Koolhaas JM, Bartolomucci A, Buwalda B, et al. Stress revisited: a critical evaluation of the stress concept. Neurosci Biobehav Rev. 2011;35:1291–301. 10.1016/j.neubiorev.2011.02.003. 10.1016/j.neubiorev.2011.02.003 PubMed DOI

Armario A, Belda X, Gagliano H, Fuentes S, Molina P, Serrano S, et al. Differential hypothalamic-pituitary-adrenal response to stress among rat strains: methodological considerations and relevance for neuropsychiatric research. Curr Neuropharmacol. 2023;21:1906–23. 10.2174/1570159X21666221129102852. 10.2174/1570159X21666221129102852 PubMed DOI PMC

Altered Balance between Vasoconstrictor and Vasodilator Systems in Experimental Hypertension