(agmatine, AGM) 1994 Li. (alpha 22adrenergic re2 ceptor, 2 2AR) (imidazoline receptor, IR) (0 4 ) Krebs2Henseleit ( K2H)

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1 , , 51 (3), Acta Physiologica Sinica 3 (, ), (agmatine, AGM) : (1) AGM ; (2), AGM (1 mmol/ L),, ; (3) L2NAME (015 mmol/ L), AGM (1 mmol/ L) ; (4) (imidazoline receptor, IR) 2 2 (alpha 22adrenergic receptor, 2 2AR) idazoxan (011 mmol/ L), AGM (1 mmol/ L), AGM 2 2AR IR, Ca 2 + : ; ; ; ; idazoxan : Q463 (agmatine, AGM) 1994 Li, (imidazoline receptor, IR) 2 2 (alpha 22adrenergic re2 [1 ceptor, 2 2AR) ] AGM [2 ], [3, ] Gao [4 ] AGM, AGM,, AGM AGM, g,,,, (0 4 ) Krebs2Henseleit ( K2H),, K2H (ph ), 4 ml/ min, (SEN23201, Nihon Kohden), 1 ms, 1 Hz, M, (MEZ28201, Nihon Kohden),,,, , Phn : , ext Fax : E2mail :

2 (RP), (OS), (APA), 0 (V max ), 50 %, 90 % 100 % (APD 50, APD 90 APD) ; 2 3, (plateau period duration, PPD) [5 ], AGM 1 h,, AGM (015 2 mmol/ L) K2H 30 min, 1, 5, 10, 15, 20, 30 min, K2H, AGM K2H 1 h, 115 mol/ L K + ( KCl 18 mmol/ L) K2H, AGM (1 mmol/ L), NOS L2NAME AGM, N G 2nitro2L2arginine methyl ester (L2NAME, 015 mmol/ L) K2H 10 min, AGM (1 mmol/ L) K2H, Idazoxan AGM idazoxan (011 mmol/ L) K2H, 10 min AGM (1 mmol/ L) K2H 113, x s x, t, F P < AGM AGM PPD, APD 50, APD 90 APD, 5 10 min 1 Table 1 Effects of AGM on the parameters of action potential in guinea pig papillary muscles RP OS APA V max / V s - 1 PPD APD 50 APD 90 APD AGM (mmol/ L) # # # # # n = 6. 3 P < 0101, 3 P < vs P < 0101, + P < vs AGM (015 mmol/ L). # # # # # P < 0101, # P < vs AGM(110 mmol/ L).

3 3 : mmol/ L AGM, PPD APD 50 ( P < 0105), ( P > 0105) ; 1 mmol/ L A GM, PPD, A PD 50, APD 90 APD ( P < 01001), RP, OS, APA V max ( P > 0105) ; AGM 2 mmol/ L, PPD, APD 50, APD 90 APD, RP, OS, APA V max ( P < 0105) ( 1 1) 1 AGM Fig11 Effects of AGM on the parameters of action potential of guinea pig papillary muscles under different conditions A. Effects of AGM on the parameters of action potential in normal papillary muscles. 1 : control ; 2 : 015 mmol/ L ; 3 : 110 mmol/ L ; 4 : 210 mmol/ L AGM. B. Effects of AGM on the paramerters of action potential in partially depolarized papillary muscles. 1 : control ; 2 : 1 mmol/ L AGM. C. Failure of L2NAME to affect the AGM2induced changes in action potential of guinea pig papillary muscles. 1 : control ; 2 : 015 mmol/ L L2NAME; 3 : L2NAME + 1 mmol/ L AGM. D. Blocking effects of idazoxan on the AGM2induced changes in action potential of guinea pig papillary muscles. 1 : control ; 2 : 011 mmol/ L idazoxan ; 3 : idazoxan + 1 mmol/ L AGM. 212 AGM K +, 1 mmol/ L AGM PPD, APD 50, APD 90 APD ( P < 01001) ; APA, OS V max ( P < 0105) ( 2 1B) 213 L2NAME AGM 015 mmol/ L L2NAME,, ( P > 0105) 10 min 1 mmol/ L AGM, PPD, APD 50, APD 90 APD ( P < 01001) ( 3 1C)

4 Table 2 Effects of AGM (1 mmol/ L) on the parameters of action potential of partially depo2 larized papillary muscles RP OS APA V max / V s - 1 PPD APD 50 APD 90 APD AGM n = 6. 3 P < 0101, 3 P < vs control. 3 L2NAME (015 mmol/ L) idazoxan (011 mmol/ L) (1 mmol/ L) Table 3 Effects of L2NAME (015 mmol/ L) and idazoxan (011 mmol/ L) on the AGM (1 mmol/ L) 2induced changes in action potential of guinea pig papillary muscles RP OS APA V max / V s - 1 PPD APD 50 APD 90 APD AGM L2NAME L2NAME + AGM # # 3 # # # # # # # # # AGM Idazoxan Idazoxan + AGM n = 6. AGM. 3 P < 0101, # # # P < 0101, 3 P < vs control. # # # P < vs L2NAME. P < 0101, P < vs 214 Idazoxan AGM idazoxan (011 mmol/ L) 10 min,, ( P > 0105) 1 mmol/ L AGM K2H, PPD, APD 50, APD 90 APD

5 3 : 325 ( P > 0105), 011 mmol/ L idazoxan 1 mmol/ L AGM ( 3 1D) 3, AGM Ca 2 + K +, Ca 2 + K +, PPD [6 ] K + K2H,, V max Ca 2 + [5 ] 1 mmol/ L AGM, OS, APA V max ; AGM Ca 2 +, PPD Ca 2 + [3 ] Gao [4 ], AGM, RP, OS, APA V max,,, AGM Na + Ishikawa [7 ], AGM NO, NOS, AGM NO, cgmp, [8 ] Galea [9 ] AGM NOS, NO NOS L2NAME AGM, AGM NO, [10 ], AGM 2 2AR IR,,, 2 2AR IR [11 IR,, ] Fuder Schwarz, 2 2AR IR [11 ] idazoxan IR 2 2AR [12 ] idazoxan, AGM, AGM 2 2AR IR, AGM 2 2AR IR, Ca 2 +, [1 ] Li G, Regunathan S, Barrow CJ, et al. Agmatine : an endogenous clonidine2displacing substances in the brain. Science, 1994, 263 : [2 ] Raasch W, Regunathan S, Li G, et al. Agmatine, the bacterial amine, is widely distributed in mammalian tis2 sue. Life Sci, 1995, 56 : [3 ] Li XT ( ), He RR ( ). Hemodynamic effects of agmatine and its cellular mechanism in anes2 thetized rats. Acta Physiol Sin ( ), 1999, 51 (2), (in Chinese with English Abstract). [ 4 ] Gao Y, Gumusel B, Koves G, et al. Agmatine : a novel endogenous vasodilator substance. Life Sci, 1995, 57 : [5 ] An RH ( ), He RR ( ). Electrophysiological effects of m2nisoldipine and nisodipine on papillary muscles of guinea pig. Acta Pharmacol Sin ( ), 1990, 11 : [6 ] He RR ( ). Cardiovascular Physiology. Beijing : People s Medical Publishing House, 1987, [ 7 ] Ishikawa T, Misonou T, Ikeno M, et al. N 2hydroxyagmatine : a novel substance causing endothelium dependent vasorelaxation. Biochem Biophs Res Commun, 1995, 214 : [8 ] Brady AJB, Warren JB, Poole2Wilson PA, et al. Nitric oxide attenuates cardiac myocyte contraction. Am J Ca 2 +

6 Physiol, 1993, 526 : H176 H182. [9 ] Galea E, Regunathan S, Eliopoulos V, et al. Inhibition of mammalian nitric oxide synthase by agmatine, an en2 dogeous polyamine formed by decarboxylation of arginine. Biochem J, 1996, 316 : [10 ] Regunathan S, Li G, Youngson C, et al. Vascular smooth muscle and endothelium express imdazoline receptors and agmatine : a novel endothelial2derived vasoactive agent? FAS ER J, 1994, 8 : A556. [11 ] Fuder H, Schwarz P. Desensitization of inhibitory prejunctional alpha222adrenoceptors and putative imidazoline receptors on rabbit heart sympathetic nerves. Naunyn2Schmiedeberg s Arch Pharmacol, 1993, 348 : [12 ] Gonzalez C, Regunathan S, Reis DJ, et al. Agmatine, an endogenous modulator of noradrenergic neurotransmis2 sion in the rat tail artery. Br J Pharmacol, 1996, 119 : Acta Physiologica Sinica Jun. 1999, 51 (3), EL ECTROPHYSIOLO GICAL EFFECTS OF AGMATINE ON GUINEA PIG PAPILLARY MUSCL ES IN VI TRO LI XIAO2TAO, HE RUI2RONG 3 ( Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang ) ABSTRACT The cardiac electrophysiological effects of agmatine (AGM) were examined in guinea pig papillary muscle using intracellular microelectrode technique. The results obtained are as follows. (1) Duration of action potential (APD) in normal papillary muscles were de2 creased by AGM in a concentration2dependent manner. (2) In partially depolarized papil2 lary muscles, amplitute of action potential, overshoot, maximal velocity of phase 0 depo2 larization and APD were depressed by AGM. (3) Pretreatment with N G 2nitro2L2arginine methyl ester (L2NAME, 015 mmol/ L) did not affect the above effects of AGM (1 mmol/ L) on papillary muscles. (4) The effects of AGM (1 mmol/ L) could be blocked com2 pletely by pretreatment with idazoxan (011 mmol/ L), an 2 2adrenoceptor ( 2 2AR) and imidazoline receptor ( IR) antagonist. All these results indicate that the effects of AGM on papillary muscles are likely due to a decrease of intracellular calcium mediated by 2 2AR and IR. Key words : agmatine ; action potential ; papillary muscle ; electrophysiology ; idazoxan 3 Correspondence to Prof1 HE Rui2Rong. Phn : , ext Fax : E2mail :

Effect of acetylcholine on the discharge of presympathetic neurons of the rostral ventrolateral medulla of rats 3

Effect of acetylcholine on the discharge of presympathetic neurons of the rostral ventrolateral medulla of rats 3 468, Dec. 2000, 52 (6) : 468 472 Acta Physiologica Sinica 3, 1 3 3,,, (, 200433 ; 1, 230000) :, (ACh) (RVLM) RVLM 35, ACh ( P < 0105), 22 M (ATR) ( P < 0105) ACh ; 7 6 (ACh N 1 N 2 ) (ACh N 1 ) ACh, RVLM