Triazolo- and tetrazolopyridazine derivatives and their hypotension and heart rate activity.

6-Chloro-, 6-morpholino- and 6-N-methylpiperazino-1,2,4-triazolo[4,3-b]- or 1,2,3,4-tetrazolo[1,5-b]pyridazines [II-VII] were synthesized from 3-chloro-6-hydrazinopyridazine [I]. Positive effect of a series of tetra- and triazolopyridazines for lowering blood-pressure without affecting the heart rate was found in tests on rats. Their lipophilicity and other properties are discussed.

Cerebrovascular effects of angiotensin converting enzyme inhibition involve large artery dilatation in rats.

Background And Purpose: The aim of the study was to selectively examine the effects of converting enzyme inhibition on the large brain arteries by using concomitant inhibition of carbonic anhydrase to cause severe dilatation of mainly parenchymal resistance vessels.

Methods: Cerebral blood flow was measured using the xenon-133 injection technique in three groups of Wistar rats either during carbonic anhydrase inhibition with acetazolamide (treatment A, n = 8), during carbonic anhydrase inhibition followed by converting enzyme inhibition with captopril 40 minutes later (treatment B, n = 10), or during carbonic anhydrase inhibition preceded by converting enzyme inhibition 20 minutes earlier (treatment C, n = 7).

Results: After treatment A, cerebral blood flow rose rapidly and stabilized within 20 minutes at an average of 220 ml/100 g.

Dose-related effects of dopamine on microcirculatory blood flow in resting and active state.

We compared the effects of low and high doses of dopamine and dobutamine (a synthetic catecholamine) on blood flow in relaxed or exercising muscles. Experiments were performed on rabbits. Blood flow in the muscles (calf) was estimated with the clearance method of radionuclide 133Xe.

Effect of thymoanaleptic agents on the course of experimental arterial hypertension and catecholamine content in tissues and urine.

Experimental hypertension was induced in rats by two methods. In the course of hypertension development the rats of experimental groups were treated with following tricyclic antidepressive agents: Imipramine, Opipramol, Amitriptylline and Nortriptylline injected in doses of 5.0 or 0.

Sesquiterpene lactones. XIX. Preliminary studies on the mode of action. Inhibition of synthesis of tumor cell protein and RNA.

The isotopic examinations of the mode of action of cytostatic active acid 8a-isobuetyric-14,15-dihydroxy-germacran-1 (10),4,11(13)-trienolide 12(6) (alatolide) have demonstrated that the compound at concentration 5-6 X 10(-5) M induces defective changes in HeLa cells resulting in the inhibition of protein synthesis in 93-8% and RNA in 91-9% and, in consequence, cell death. At lower concentrations 2-8 X 10(-6) M, the compound inhibits protein synthesis in 73% and RNA in 5-7%. The direct influence of alatolide on DNA synthesis is doubtful.