MODELING HEMODYNAMIC PROFILES BY TELEMETRY IN THE RAT - A STUDY WITH A(1) AND A(2A) ADENOSINE AGONISTS

The newly developed radiotelemetry system offers a number of advantage s for the measurement of blood pressure and heart rate in laboratory a nimals. However, no available statistical methods permit valid use of the many data gathered with this continuous recording of hemodynamic p arameters. This study describes elaboration and testing of mathematica l functions as applied to the measurement of the effects of drugs on b lood pressure and heart rate in spontaneously hypertensive rats. We us ed parametric functions analogous to those for pharmacokinetic studies . Curve fitting is in fact the only approach that provides reasonable estimates of hemodynamic kinetic constants. Nonlinear functions were a ssessed by analyzing telemetric hemodynamic effects induced by three a denosine receptor agonists with different selectivity for the A(1) or A(2a) receptor. After acute administration in conscious rats, the A(1) agonist 2-chloro-N-6-cyclopentyladenosine induced dose-related hypote nsion (eg, 0.03 mg/kg; peak, -70 mm Hg; time to peak, 0.34 hour) and b radycardia (eg, 0.03 mg/kg; peak, -186 beats per minute [bpm]; time to peak, 0.38 hour). The A(2a) agonist 2-hexynyl-5'-N-ethylcarboxamidoad enosine induced dose-related hypotension (eg, 0.003 mg/kg; peak, -36 m m Hg; time to peak, 0.32 hour) with reflex tachycardia (eg, 0.003 mg/k g; peak, 152 bpm; time to peak, 0.35 hour). The nonselective adenosine agonist 5'-N-ethylcarboxamidoadenosine (0.1 mg/kg) induced hypotensio n (peak, -75 mm Hg; time to peak, 2.2 hours) and bradycardia followed by tachycardia (first peak, -131 bpm; time to peak, 1.26 hours; second peak, 123 bpm; time to peak, 13.9 hours). With this model, other para meters, such as persistence (eg, half-life) or amount (eg, area under the curve) of the effects, can also be evaluated. Finally, the telemet ry system permits precise characterization of the hemodynamic profile of different classes of cardiovascular drugs.