Modification of XXXX - and @entity11502 - induced changes by @entity460 antagonists in the peripheral circulation of anaesthetized @entity95 .

@entity7236 @entity308 @entity1855 @entity95 @entity1951 @entity16941 @entity376 @entity460 @entity468 @entity11502
Investigations into the site of vasodilator and antivasoconstrictor activity of @entity460 antagonists previously performed in @entity468 were extended to a second species, barbiturate-anaesthetized @entity95 , and a second vasoconstrictor agent, @entity1951 . The @entity7236 derivative @entity16941 (code name PY 108-068; 10, 30 and 100 micrograms kg-1 i.v.) showed systemic haemodynamic effects comparable to those seen in @entity468 at half these doses. @entity16941 effected regional vasodilatation (measured with tracer microspheres) in the heart, brain and skeletal muscles as in @entity468 . Only the vessels of the adrenals (dilated in @entity95 but not in @entity468 ), and the kidneys and skin (constricted in @entity95 but not in @entity468 ) responded differently to @entity16941 . @entity11502 (A II; 0.15 and 1.5 micrograms kg-1 min-1) constricted the same vascular beds in @entity95 as in @entity468 , namely the heart, kidneys, small intestine, pancreas, spleen, skin and arterio-venous shunts (inferred from microspheres reaching the lungs), the only exceptions being the vessels of the stomach and liver (constriction only in @entity468 ) and the adrenals (constriction only in @entity95 ). @entity16941 (30 and 100 micrograms kg-1) attenuated the A II-induced vasoconstriction in the same vascular beds in @entity95 as in @entity468 including the kidneys, which were constricted after administration of the antagonist alone. These results indicate surprisingly small species differences for the vasodilator effects of @entity16941 as well as the attenuation of the vasoconstrictor effects of A II. @entity376 - @entity1951 (2 and 50 mu kg-1 min-1) did not increase blood pressure in anaesthetized @entity95 but dose-dependently lowered heart rate, cardiac output, total peripheral conductance and myocardial contractile force (measured with a strain gauge). @entity1951 constricted all peripheral vascular beds dose-dependently, except for those of the kidney and liver. The effects of @entity1951 persisted in the animals infused with placebo solution. @entity16941 (30 and 100 micrograms kg-1), but not @entity1855 (300 and 1000 micrograms kg-1) reversed the @entity1951 -induced @entity308 and decrease in cardiac output. This probably also explains most of the apparent differences between the effects of the two @entity460 antagonists on the peripheral circulation. Both @entity460 antagonists diminished the @entity1951 constriction in most vascular beds except those of the spleen, skin and arterio-venous shunts. Most of the effects were dose-related but not strictly competitive, as far as this can be judged based on two doses of agonist and antagonist. 9 As with A II the effects of @entity1951 were diminished in vascular beds not normally dilated by @entity460 antagonists. 10 @entity460 antagonists display two typical patterns of activity. The vasodilator pattern consists of dilatation of the vesels of the heart, brain and, to a degree varying with the agents, skeletal muscle. The antivasoconstrictor effects occur in some but not all of the vessels constricted by the constrictor agent, vasoconstriction of the spleen, skin and arterio-venous shunts being resistant to the action of @entity460 antagonists. The pattern of antivasoconstrictor activity appears to depend on the constrictor compound used, inasmuch as such agents constrict different vascular beds.
