The effect of chemical sympathectomy on cardiovascular parameters and the compensatory role of adrenal hormones, the renin-angiotensin system, and cardiovascular sensitivity to vasoconstrictors were studied in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. Sympathectomy was induced in 20-week-old rats by daily intraperitoneal guanethidine administration (30 mg/kg b.w.) for 2 weeks. Basal blood pressure (BP), heart rate (HR), and restraint stress-induced cardiovascular changes were measured by radiotelemetry. The BP response to catecholamines was determined in rats with implanted catheters. Sympathectomy decreased BP only transiently, and after 14-day guanethidine treatment, BP returned to basal values in both strains. Sympathectomy permanently lowered HR, improved baroreflex sensitivity, and decreased the low-frequency domain of systolic blood pressure variability (a marker of vascular sympathetic activity). Guanethidine also attenuated the BP and HR responses to restraint stress. On the other hand, the BP response to catecholamines was augmented in sympathectomized rats, and this was not due to the de novo synthesis of vascular adrenergic receptors. Sympathectomy caused adrenal enlargement, enhanced the expression of adrenal catecholamine biosynthetic enzymes, and elevated plasma adrenaline levels in both strains, especially in WKY rats. Guanethidine also increased the plasma levels of aldosterone and corticosterone in WKY rats only. In conclusion, sympathectomy produced a transient decrease in BP, a chronic decrease in HR and improvement in baroreflex sensitivity. The effect of sympathectomy on BP was counteracted by increased vascular sensitivity to catecholamines in WKY rats and SHRs and/or by the enhanced secretion of adrenal hormones, which was more pronounced in WKY rats.

Faculty of Science Charles University Prague Czech Republic

Institute of Physiology Czech Academy of Sciences Prague Czech Republic

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Guyenet PG. The sympathetic control of blood pressure. Nat Rev Neurosci. 2006;7:335–46. PubMed

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

Cassis LA, Stitzel RE, Head RJ. Hypernoradrenergic innervation of the caudal artery of the spontaneously hypertensive rat: an influence upon neuroeffector mechanisms. J Pharm Exp Ther. 1985;234:792–803.

Vavřínová A, Behuliak M, Bencze M, Vaněčková I, Zicha J. Which sympathoadrenal abnormalities of adult spontaneously hypertensive rats can be traced to a prehypertensive stage? Hypertens Res. 2019;42:949–59. PubMed

Head RJ. Hypernoradrenergic innervation: its relationship to functional and hyperplastic changes in the vasculature of the spontaneously hypertensive rat. Blood Vessels. 1989;26:1–20. PubMed

de Champlain J. Pre- and postsynaptic adrenergic dysfunctions in hypertension. J Hypertens Suppl. 1990;8(Suppl7):S77–85. PubMed

Lee RM, Triggle CR, Cheung DW, Coughlin MD. Structural and functional consequence of neonatal sympathectomy on the blood vessels of spontaneously hypertensive rats. Hypertension. 1987;10:328–38. PubMed

Lee RM, Borkowski KR, Leenen FH, Tsoporis J, Coughlin M. Combined effect of neonatal sympathectomy and adrenal demedullation on blood pressure and vascular changes in spontaneously hypertensive rats. Circ Res. 1991;69:714–21. PubMed

Korner P, Bobik A, Oddie C, Friberg P. Sympathoadrenal system is critical for structural changes in genetic hypertension. Hypertension. 1993;22:243–52. PubMed

Ferrari AU, Daffonchio A, Franzelli C, Mancia G. Potentiation of the baroreceptor-heart rate reflex by sympathectomy in conscious rats. Hypertension. 1991;18:230–5. PubMed

Finch L, Leach GD. The contribution of the sympathetic nervous system to the development and maintenance of experimental hypertension in the rat. Br J Pharm. 1970;39:317–24.

Yamori Y, Yamabe H, De Jong W, Lovenberg W, Sjoerdsma A. Effect of tissue norepinephrine depletion by 6-hydroxydopamine on blood pressure in spontaneously hypertensive rats. Eur J Pharm. 1972;17:135–40.

Johnson EM Jr., O’Brien F. Evaluation of the permanent sympathectomy produced by the administration of guanethidine to adult rats. J Pharm Exp Ther. 1976;196:53–61.

Franco-Colín M, Villanueva I, Piñón M, Racotta R. The effects of sympathectomy and dexamethasone in rats ingesting sucrose. Int J Biol Sci. 2006;2:17–22. PubMed 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. PubMed

Johnson EM Jr., Manning PT. Guanethidine-induced destruction of sympathetic neurons. Int Rev Neurobiol. 1984;25:1–37. PubMed

Lo M, Julien C, Barres C, Medeiros I, Allevard AM, Vincent M, et al. Blood pressure maintenance in hypertensive sympathectomized rats. II. Renin-angiotensin system and vasopressin. Am J Physiol. 1991;261(4 Pt 2):R1052–6. PubMed

Fleming WW. Postjunctional supersensitivity: a cellular homeo-static mechanism. Trends Pharm Sci. 1981;2:152–4.

Bencze M, Behuliak M, Vavřínová A, Zicha J. Altered contractile responses of arteries from spontaneously hypertensive rat: the role of endogenous mediators and membrane depolarization. Life Sci. 2016;166:46–53. PubMed

Vaněčková I, Vokurková M, Rauchová H, Dobešová Z, Pecháňová O, Kuneš J, et al. Chronic antioxidant therapy lowers blood pressure in adult but not in young Dahl salt hypertensive rats: the role of sympathetic nervous system. Acta Physiol (Oxf). 2013;208:340–9.

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(Suppl3):S79–81. PubMed

Kunes J, Dobesová Z, Zicha J. Altered balance of main vasopressor and vasodepressor systems in rats with genetic hypertension and hypertriglyceridaemia. Clin Sci (Lond). 2002;102:269–77.

Zicha J, Dobešová Z, Behuliak M, Pintérová M, Kuneš J, Vaněčková I. Nifedipine-sensitive blood pressure component in hypertensive models characterized by high activity of either sympathetic nervous system or renin-angiotensin system. Physiol Res. 2014;63:13–26. PubMed

de la Torre JC, Surgeon JW. Histochemical fluorescence of tissue and brain monoamines: results in 18 min using the sucrose-phosphate-glyoxylic acid (SPG) method. Neuroscience. 1976;1:451–3. PubMed

Vavřínová A, Behuliak M, Zicha J. The importance of the selection of appropriate reference genes for gene expression profiling in adrenal medulla or sympathetic ganglia of spontaneously hypertensive rat. Physiol Res. 2016;65:401–11. PubMed

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. PubMed PMC

Chiu EK, McNeill JR. Role of autonomic function in the antihypertensive effect of vasopressin withdrawal in spontaneous hypertension. Am J Hypertens. 1992;5:187–92. PubMed

Head RJ, Cassis LA, Robinson RL, Westfall DP, Stitzel RE. Altered catecholamine contents in vascular and nonvascular tissues in genetically hypertensive rats. Blood Vessels. 1985;22:196–204. PubMed

Benarroch EE, Schmelzer JD, Ward KK, Nelson DK, Low PA. Noradrenergic and neuropeptide Y mechanisms in guanethidine-sympathectomized rats. Am J Physiol. 1990;259(2 Pt 2):R371–5. PubMed

Kamikihara SY, Mueller A, Lima V, Akinaga J, Nojimoto FD, Castilho A, et al. alpha1-Adrenoceptors in proximal segments of tail arteries from control and reserpinised rats. Naunyn Schmiedebergs Arch Pharm. 2007;376:117–26.

Rizzoni D, Perlini S, Mircoli L, Porteri E, Franzelli C, Castellano M, et al. Enhanced vascular reactivity in the sympathectomized rat: studies in vivo and in small isolated resistance arteries. J Hypertens. 2000;18:1041–9. PubMed

Colucci WS, Gimbrone MA Jr., McLaughlin MK, Halpern W, Alexander RW. Increased vascular catecholamine sensitivity and alpha-adrenergic receptor affinity in female and estrogen-treated male rats. Circ Res. 1982;50:805–11. PubMed

Malheiros-Lima MR, Pires W, Fonseca IAT, Joviano-Santos JV, Ferreira AJ, Coimbra CC, et al. Physical exercise-induced cardiovascular and thermoregulatory adjustments are impaired in rats subjected to cutaneous artery denervation. Front Physiol. 2018;9:74 PubMed PMC

Head GA. Baroreflexes and cardiovascular regulation in hypertension. J Cardiovasc Pharm. 1995;26(Suppl2):S7–16.

Mircoli L, Fedele L, Benetti M, Bolla GB, Radaelli A, Perlini S, et al. Preservation of the baroreceptor heart rate reflex by chemical sympathectomy in experimental heart failure. Circulation. 2002;106:866–72. PubMed

Dyke AC, Angus JA, Korner PI. A functional study of the development of the cardiac sympathetic neuroeffector junction in the SHR. J Hypertens. 1989;7:345–53. PubMed

Tipton CM, Sturek MS, Oppliger RA, Matthes RD, Overton JM, Edwards JG. Responses of SHR to combinations of chemical sympathectomy, adrenal demedullation, and training. Am J Physiol. 1984;247(1 Pt 2):H109–18. PubMed

Goldstein DS, McCarty R, Polinsky RJ, Kopin IJ. Relationship between plasma norepinephrine and sympathetic neural activity. Hypertension. 1983;5:552–9. PubMed

Qiu J, Nelson SH, Speth RC, Wang DH. Regulation of adrenal angiotensin receptor subtypes: a possible mechanism for sympathectomy-induced adrenal hypertrophy. J Hypertens. 1999;17:933–40. PubMed

Kvetnansky R, Weise VK, Thoa NB, Kopin IJ. Effects of chronic guanethidine treatment and adrenal medullectomy on plasma levels of catecholamines and corticosterone in forcibly immobilized rats. J Pharm Exp Ther. 1979;209:287–91.

Grisk O, Rose HJ, Lorenz G, Rettig R. Sympathetic-renal interaction in chronic arterial pressure control. Am J Physiol Regul Integr Comp Physiol. 2002;283:R441–50. PubMed

Skrzypecki J, Gawlak M, Huc T, Szulczyk P, Ufnal M. Renal denervation decreases blood pressure and renal tyrosine hydroxylase but does not augment the effect of hypotensive drugs. Clin Exp Hypertens. 2017;39:290–4. PubMed

Kubzansky LD, Adler GK. Aldosterone: a forgotten mediator of the relationship between psychological stress and heart disease. Neurosci Biobehav Rev. 2010;34:80–6. PubMed

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