Effects of proadrenomedullin N-terminal 20 peptide and calcitonin on isolated perfused rat hearts/Izole perfuze sican kalpleri uzerinde proadrenomedullin N-terminal 20 peptit ve kalsitonin'in etkileri

• Published in: Anadolu kardiyoloji dergisi : AKD Vol. 9; no. 3; p. 176
• Main Authors: Kaygisiz, Ziya, Ozden, Hilmi, Erkasap, Nilufer, Koken, Tulay, Gunduz, Tarik, Ikizler, Murat, Kural, Tugrul
• Format: Journal Article
• Language: English
• Published: KARE Publishing 01.06.2009
• Subjects: Heart beat
• ISSN: 1302-8723; 1308-0032

Objective: There are evidences that proadrenomedullin N-terminal 20 peptide (PAMP) and calcitonin may be involved in cardiovascular function. Therefore, we studied effects of rat PAMP and human PAMP as well as rat calcitonin and salmon calcitonin on coronary perfusion pressure, heart rate and contractile force. Methods: Isolated rat hearts were perfused under constant flow condition and rat PAMP (1.10 and 100 nM), human PAMP (1,10 and 100 nM), rat calcitonin (10.100 and 1000 nM) or salmon calcitonin (10.100 and 1000 nM) were infused to the hearts. Coronary perfusion pressure, heart rate, left ventricular developed pressure and +dP/[dt.sub.max] were measured. Statistical analysis was performed using repeated measures ANOVA and Bonferroni posthoc tests. Results: Rat PAMP (1.10 and 100 nM) did not alter perfusion pressure. However, it increased heart rate from 257.83 ± 23.89 to 282±24.98 beats/min (p<0.001), from 259.83±25.05 to 289.8+19.5 beats/min (p<0.001) and from 249.66±19.19 to 280.50±25.26 beats/min (p<0.001) for 1.10 and 100 nM, respectively. Rat PAMP decreased left ventricular developed pressure from 90.5+18.5 to 79±15.3 mmHg (p<0.05), from 88.00±10.12 to 73.00±12.38 mmHg (p<0.05) and from 79.83±8.98 to 64.83 ±10.12 mmHg (p<0.05) for 1.10 and 100 nM, respectively. The peptide also decreased +dP/[dt.sub.max] from 3710.5±370.6 to 3223.8+261.1 mmHg s"1 (p<0.001), from 3683.16+327.27 to 3040.6±423.8 mmHg [s.sup.-1] (p<0.01) and from 3746.16±315.76 to 3009.83±204.64 mmHg [s.sup.-1] (p<0.001) for 1.10 and 100 nM, respectively. Rat calcitonin (10.100 and 1000 nM) did not change perfusion pressure but it decreased heart rate from 269.16±22.6 to 253.6±22.84 beats/min (p<0.05), from 263.8±27.3 to 247.00±36.63 beats/min (p<0.05) and from 285.0±32.4 to 264.00±39.83 beats/min (p<0.01) for 10.100 and 1000 nM, respectively. Rat calcitonin did not significantly affect left ventricular developed pressure. Human PAMP or salmon calcitonin did not change perfusion pressure, heart rate and left ventricular developed pressure. Conclusion: We conclude that rat PAMP may induce positive chronotropic and negative inotropic effect while rat calcitonin may produce a negative chronotropic effect. Human PAMP or salmon calcitonin could not alter perfusion pressure, heart rate and contractility in isolated, perfused rat hearts. (Anadolu Kardiyol Derg 2009; 9:176-82) Key words: Proadrenomedullin N-terminal 20 peptide, calcitonin, perfusion pressure, heart rate, contractility OZET Amac: Proadrenomedullin N-terminal 20 Peptit'in (PAMP) ve kalsitoninin kardiyovaskulerfonksiyonda ise karisabilecegi hakkinda kanitlar vardir. Bu nedenle sican PAMP'in, insan PAMP'in, sican kalsitonin'in ve somon kalsitonin'in koroner perfuzyon basincina, dakikada kalp atim sayisina ve kasilma kuvvetine etkilerini arastirdik. Yontemler: izole sican kalpleri sabit akim durumunda perfuze edildi ve sican PAMP (1.10 ve 100 nM), insan PAMP (1.10 ve 100 nM), sican kalsitonin (10.100 ve 1000 nM) veya somon kalsitonin (10.100 ve 1000 nM) kalplere verildi. Koroner perfuzyon basinci, dakikada kalp atim sayisi, sol ventrikulun gelistirdigi basinc ve +dP/[dt.sub.max] olculdu. Istatistiksel analiz tekrarlanan olcumler icin ANOVA ve Bonferroni testleri kullanilarak yapildi. Bulgular: Sican PAMP (1.10 ve 100 nM) perfuzyon basincini degistirmedi. Fakat dakikada kalp atim sayisini 1.10 ve 100 nM dozlarinda sirasi ile 257.83±23.89'dan 282.00±24.98 atim/dakika'ya (p<0.001), 259.83±25.05'dan 289.83±19.5 atim/dakika'ya (p<0.001) ve 249.66±19.19'dan 280.50±25.26 atim/dakika'ya (p<0.001) artirdi. Sican PAMP sol ventrikulun gelistirdigi basinci 1.10 ve 100 nM dozlarinda sirasi ile 90.5±18.5'dan 79.0±15.3 mmHg'ya (p<0.05), 88.00±10.12'dan 73±12.38 mmHg'ya (p<0.05) ve 79.83±8.98'dan 64.83+10.12 mmHg'ya (p<0.05) azaltti. Bu peptit +dP/[dt.sub.max] degerlerini de 1.10 ve 100 nM dozlarinda sirasi ile 3710.5±370.6'dan 3223.8±261.1 mmHg [s.sup.-1]'ya (p<0.001), 3683.16±327.27'dan 3040.6±423.8 mmHg s^'ya (p<0.01) ve 3746.16±315.76'dan3009.83±204.64mmHg [s.sup.-1]'ya (p<0.001) azaltti. Sican kalsitonin (10,100 ve 1000 nM) perfuzyon basincini degistirmedi. Fakat dakikada kalp atim sayisini 10.100 ve 1000 nM dozlarinda sirasi ile 269.16±22.60'dan 253.60±22.84 atim/dakika'ya (p<0.05), 263.83±27.30'dan 247.00±36.63 atim/dakika'ya (p<0.05) ve 285.0±32.4'dan 264.00±39.83 atim/dakika'ya (p<0.01) azaltti. Sican kalsitonin sol ventrikulun gelistirdigi basinci anlamli olarak etkilemedi. Insan PAMP veya somon kalsitonin perfuzyon basincini, dakikada kalp atim sayisini ve sol ventrikulun gelistirdigi basinci degis tirmedi. Sonuc: izole perfuze sican kalplerinde sican PAMP pozitif kronotrop ve negatif inotrop sican kalsitonin ise negatif kronotrop etki yapabilir, insan PAMP'in veya somon kalsitoninin perfuzyon basinci, dakikada kalp atim sayisi ve kasilma kuvveti uzerinde etkisi olmadigi sonucuna varilmistir. (Anadolu Kardiyol Derg 2009; 9: 176-82)