HYPOTENSIVE AND VASODILATOR ACTIONS OF SK&F 24260, A NEW DIHYDROPYRIDINE DERIVATIVE

Article date: November 1974

By: R. FIELDEN, D.A.A. OWEN, E.M. TAYLOR in Volume 52, Issue 3, pages 323-332

The blood pressure of conscious normotensive, Goldblatt‐hypertensive and genetic‐hypertensive rats and normotensive dogs was lowered by SK&F 24260 (1,4‐dihydro‐2,6‐dimethyl‐4‐(2‐trifluormethylphenyl)‐3,5‐pyridinedicarboxylic acid diethyl ester).

Tachycardia always accompanied the hypotension. In rats propranolol abolished the tachycardia but in dogs there was only a small reduction in the heart rate response.

In conscious dogs there was an increase in left ventricular output and a marked fall in total peripheral resistance.

SK&F 24260 dilated resistance vessels in rat hindquarters. Dilatation was caused by doses of SK&F 24260 some 50 times smaller than those of hydrallazine.

In preparations of cat skeletal muscle and intestinal vascular beds SK&F 24260 selectively dilated resistance vessels in preference to capacitance vessels and resembled hydrallazine rather than papaverine which has no such selectivity.

Pre‐capillary sphincter vessels were also dilated by SK&F 24260. Changes in fluid equilibrium caused by SK&F 24260 were consistent with selective dilatation of resistance vessels.

The blood pressure of conscious normotensive, Goldblatt‐hypertensive and genetic‐hypertensive rats and normotensive dogs was lowered by SK&F 24260 (1,4‐dihydro‐2,6‐dimethyl‐4‐(2‐trifluormethylphenyl)‐3,5‐pyridinedicarboxylic acid diethyl ester).

Tachycardia always accompanied the hypotension. In rats propranolol abolished the tachycardia but in dogs there was only a small reduction in the heart rate response.

In conscious dogs there was an increase in left ventricular output and a marked fall in total peripheral resistance.

SK&F 24260 dilated resistance vessels in rat hindquarters. Dilatation was caused by doses of SK&F 24260 some 50 times smaller than those of hydrallazine.

In preparations of cat skeletal muscle and intestinal vascular beds SK&F 24260 selectively dilated resistance vessels in preference to capacitance vessels and resembled hydrallazine rather than papaverine which has no such selectivity.

Pre‐capillary sphincter vessels were also dilated by SK&F 24260. Changes in fluid equilibrium caused by SK&F 24260 were consistent with selective dilatation of resistance vessels.

DOI: 10.1111/j.1476-5381.1974.tb08599.x

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