Abstract
Purpose. The hemodynamic profiles of KRN2391-induced hypotension have been reported to be a hyperdynamic state. However, the endocrine effects of KRN2391-induced hypotension remain to be elucidated. We investigated the endocrine and metabolic effects of KRN2391-induced hypotension on the plasma concentrations of catecholamines, aldosterone, cortisol, glucose, and lactic acid and on plasma renin activity.
Methods. Eight dogs were anesthetized with 087% halothane in oxygen. After a baseline period, mean arterial pressure (MAP) was lowered to 60 mmHg for 60min by the infusion of KRN2391.
Results. KRN2391-induced hypotension resulted in a 50% decrease (P<0.01) in MAP due to a 80% reduction (P<0.01) in systemic vascular resistance associated with a 224% increase (P<0.01) in cardiac index. Plasma norepinephrine concentrations increased (P<0.01) after 60 min of hypotension. Plasma epinephrine concentrations and plasma renin activity both increased (P<0.05) during the hypotensive period. Plasma aldosterone concentrations remained unchanged during the hypotensive period, but then increased (P<0.05) after termination of KRN2391. Plasma cortisol concentrations remained unchanged throughout the observation period. Plasma glucose concentrations increased (P<0.01) during the hypotensive period. Plasma lactic acid concentrations increased (P<0.01) throughout the observation period.
Conclusion. KRN2391-induced hypotension activates the sympathetic nervous system and consequently may modulate the renin-angiotensin-aldosterone axis and carbohydrate metabolism.
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References
Kashiwabara T, Nakajima S, Izawa T, Fukushima H, Nishikori K (1991) Characteristics of KRN2391, a novel vasodilator, compared with those of cromakalim, pinacidil and nifedipine in rat aorta. Eur J Pharmacol 196:1–7
Ishibashi T, Hamaguchi M, Imai S (1992) Vasodilating properties of KRN2391: structural basis of a new pyridine-type potassium channel opener with a nitrate moiety. Naunyn Schmiedebergs Arch Pharmacol 346:94–101
Ogawa N, Jinno Y, Kaneta S, Harada K, Fukata Y, Fukushima H (1993) Hemodynamic profile of KRN2391, a novel vasodilator, in anesthetized dogs. J Cardiovasc Pharmacol 21:874–882
Ogawa N, Kaneta S, Jinno Y, Kasai H, Nishikori K, Fukushima H (1992) Comparative cardiovascular effects of KRN2391 and other coronary vasodilators in anesthetized open-chest dogs. Arch Int Pharmacodyn 318:36–46
Takeuchi A, Harada K, Miwa A, Jinno Y, Kaneta S, Yokoyama T, Ogawa N (1994) Effect of KRN2391 on canine ventricular arrhythmia models. Gen Pharmacol 25:53–60.
Takeda S, Inada Y, Ozawa Y, Nakamizo N, Tomaru T (1995) Hemodynamic effects of KRN2391 (potassium channel opener) in halothane-anesthetized dogs. J Anesth 9:176–181
Tashiro N, Takeda S (1997) Possible evaluation of hemodynamic effects of the potassium channel opener KRN2391 on induced hypotension in dogs. J Anesth 11:136–140
Cook NS (1988) The pharmacology of potassium channels and their therapeutic potential. Trends Pharmacol Sci 9:21–28
Goldstein DS, McCarty R, Polinsky RJ, Kopin IJ (1983) Relationship between plasma norepinephrine and sympathetic neural activity. Hypertension 5:552–559
Seagard JL, Hopp FA, Donegan JH, Kalbfleisch JH, Kampine JP (1982) Halothane and the carotid sinus reflex: evidence for multiple sites of action. Anesthesiology 57:191–202
Silverberg AB, Shah SD, Haymond MW, Cryer PE (1978) Norepinephrine: hormone and neurotransmitter in man. Am J Physiol 234(Endocrinol Metab Gastrointest Physiol 3)E252-E256
Honda T, Ninomiya I (1988) Changes in AdSNA and arterial catecholamines to coronary occlusion in cats. Am J Physiol 255 (Heart Circ Physiol 24):H704-H710
Takeda S, Inada Y, Nakamizo N, Nomura N, Tomaru T, Negishi H, Hosoyamada A (1991) A comparison of the endocrine effects of hypotension induced by nicardipine with those by sodium nitroprusside in dogs (in Japanese with English abstract). Masui (Jpn J Aensthesiol) 40:1063–1069
Knight PR, Lane GA, Hensinger RN, Bolles RS, Bjoraker DG (1983) Catecholamine and renin-angiotensin response during hypotensive anesthesia induced by sodium nitroprusside or trimetaphan camsylate. Anesthesiology 59:248–253
Zäll S, Edén E, Winsö I, Volkmann R, Sollevi A, Ricksten S-E (1990) Controlled hypotension with adenosine or sodium nitroprusside during cerebral aneurysm surgery: effects on renal hemodynamics, excretory function, and renin release. Anesth Analg 71:631–636
Lagerkranser M, Sollevi A, Irestedt L, Tidgren B, Andreen M (1985) Renin release during controlled hypotension with sodium nitroprusside, nitroglycerin and adenosine: a comparative study in the dog. Acta Anaesthesiol Scand 29:45–49
Bernard J-M, Pinaud M, François T, Babin M, Macquin-Mavier I, Letenneur J (1991) Deliberate hypotension with nicardipine or nitroprusside during total hip arthroplasty. Anesth Analg 73:341–345
Davis JO, Freeman RH (1976) Mechanisms regulating renin release. Physiol Rev 56:1–56
Hackenthal E, Taugner R (1986) Hormonal signals and intracellular meassengers for renin secretion. Mol Cell Endocrinol 47:1–12
Abe Y, Yukimura T, Iwao H, Mori N, Okahara T, Yamamoto K (1983) Effects of EDTA and verapamil on renin release in dogs. Jpn J Pharmacol 33:627–633
Henrich WI, Campbell WB (1986) Importance of calcium in renal renin release. Am J Physiol 251(Endocrinol Metab 14):E98-E103
Park CS, Han DS, Fray JCS (1981) Calcium in the control of renin secretion: Ca2+ influx as an inhibitory signal. Am J Physiol 240 (Renal Fluid Electrolyte Physiol 9):F70-F74
Churchill PC (1985) Second messengers in renin release. Am J Physiol 249(Renal Fluid Electrolyte Physiol 18):F175-F184
Cohen PJ (1975) More on lactate. Anesthesiology 43:614–616
Clutter WE, Bier DM, Shah SD, Cryer PE (1980) Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man. J Clin Invest 66:94–101
Takeda S, Ozawa Y, Inada Y, Tomaru T, Hosoyamada A (1996) The effect of KRN2391- and nicardipine-induced hypotension on splanchnic organ blood flow. Anesthesiology 85:A592
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Takeda, S., Iizuka, H., Miyamoto, H. et al. Effects of KRN2391-induced hypotension on the endocrine system and carbohydrate metabolism in halothane-anesthetized dogs. J Anesth 12, 69–75 (1998). https://doi.org/10.1007/BF02480775
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DOI: https://doi.org/10.1007/BF02480775