Effects of proadrenomedullin N-terminal 20 peptide and calcitonin on isolated perfused rat hearts.

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/dtmax 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/dtmax 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-1 (p<0.01) and from 3746.16+/-315.76 to 3009.83+/-204.64 mmHg s-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.