Figure 6-Polygraph records showing, from below upward,
the effects of himachalol and papaverine on blood pressure, mean femoral blood flow, and pulsatile femoral blood flow in an anesthetized cat. Key: A, control response to 0.25 ml of alcohol alone 30 see after intravenous injection; H , hypotension a n d increase in the mean a n d pulsatile femoral blood flow 30 sec after intravenous injection of 5 mglkg of himachalol dissolved in 0.25 ml of alcohol; a n d P, marked hypotension a n d increase in the mean a n d pulsatile femoral blood flow following injection of papaverine (2 mg/kg iv).
There is a qualitative difference in the effect of the two compounds on guinea pig bronchial muscle. Himachalol causes constriction of bronchial muscle and papaverine causes relaxation. The constriction caused by himachalol cannot be blocked by pyrilamine, an antihistaminic agent, and, therefore, it seems unlikely that the constriction is due to release of histamine (Fig. 5). It is also unlikely that pulmonary congestion caused by himachalol would bring about bronchoconstriction by diminishing air inflow through bronchial tubes since papaverine causes greater vasodilation but does not cause any increase in bronchial resistance. Bronchoconstriction probably is the result of a directly stimulating action of himachalol in some unknown way.
Himachalol, like papaverine, produces systemic hypotension and peripheral vasodilation. The hypotensive effect is not mediated by cholinergic or histaminic receptor sites since the hypotension remains unaffected following pretreatment with atropine and pyrilamine. A stimulation of 8-adrenergic receptors by himachalol can also be ruled out due to the absence of any tachycardia or relaxant effect on the bronchial musculature. The hypotension is unlikely to be due to a cardiac effect either, since there is no significant effect on heart rate in intact animals and only a mild inhibitory effect on the isolated auricle. The hypotension, therefore, appears to result mainly from a decrease in the peripheral resistance due to