Timed dose-response relationship analysis of pressor and hypotensive action of drugs

The graded and timed dose-response relationship (TDRR) of pressor and hypotensive action by i.v. norepinephrine (NE) and sodium nitroprusside (SNP) respectively were studied in 13 male rabbits. The arterial blood pressure was dose-dependently raised by NE 0.98-125 micrograms.kg-1 and lowered by SNP 7.81-500 micrograms.kg-1 (F test, P < 0.01). The comparisons between dose groups showed that the latency and duration of both NE and SNP action were dose-dependent (P < 0.01), and the data were nonlinear least-square fit to the hyperbolic 4-parameter model II (HFPM): Y = cs + 1/(magnitude of ln X - a)s + b, weighting the square error inversely with the square of Sx. In duration data, the regression equation was Y = 462.9906/(6.6924 - ln X) 0.9701 - 24.3335 for NE and Y = 374935.1632/(12.8573 - ln X)3.3975 - 3.139 for SNP action, while in latency, Y = 345.5548/(ln X + 7.8428)2.4056 + 3.9809 and Y = 17.9595/(ln X - 0.4898)0.5763 + 1.4768 for NE and SNP, respectively. Moreover, the positive correlation was found between the peak-reaching time or average rising rate of the drug actions and the dose groups (P < 0.01). The results proved that the hyperbolic type of TDRR existed in the pressor and hypotensive action by iv drugs, and the HFPM was the common mathematical model to fit different TDRR data.