Identification of ethanolamine in rat and gerbil brain tissue extracts by NMR spectroscopy.

Some NMR resonances which have previously been observed but not identified in mammalian brain tissue extracts have been shown to arise from ethanolamine. This conclusion is drawn from a systematic study of the perchloric acid extracts of rodent brain tissue in which several NMR experiments were used to assign the peaks unambiguously. The extraction procedure used in this work gave samples with highly reproducible spectra, and ethanolamine was observed in all our extract samples.

Anatomic variation of the middle cerebral artery in the Sprague-Dawley rat.

Background And Purpose: The aim of this study was to record and analyze the anatomy of the middle cerebral artery in the rat in an attempt to identify a potential source of variation of quantitative infarct measurements in commonly used models of focal cerebral ischemia.

Methods: Over a period of 22 months, as part of ongoing studies, we routinely induced focal cerebral ischemia in 263 Sprague-Dawley rats. This was achieved by permanent occlusion of a length of the right middle cerebral artery approximately 1 to 5 mm distal to the point at which it traverses the rhinal fissure combined with 60 minutes of bilateral common carotid occlusion.

The involvement of calcium and protein kinase C in modulating agonist-stimulated chemotaxis of human neutrophils.

Chemotaxis of human neutrophils in response to a gradient of the chemotactic peptide, fmet-leu-phe (FMLP), was measured by the under-agarose technique. The dose-response curve for FMLP was biphasic; low concentrations were stimulatory, and the response was reduced at higher concentrations. The response to FMLP was partially inhibited (about 50%) in the absence of extracellular Ca2 (EGTA added).

Distensibility of single capillaries and venules in the rat and frog mesentery.

The distensibility characteristics of single microvessels in the mesentery of frogs and rats has been determined by a new technique capable of resolving a change in radius of about 0.01 micron in vivo. Two water insoluble immiscible oils were micro-injected into occluded segments of the vessels.

Dynamic compliance of single perfused frog mesenteric capillaries and rat venules: a filtration coefficient correction.

The compliance of microvessels produces a potential source of error in the measurement of hydraulic conductance, regardless of which method is used. The compliance characteristics of rat and frog microvessels, in vivo, was studied using a two oil technique capable of measuring changes in radius of 0.01 micron at intervals of 0.

Evidence for homogeneity of thromboxane A2 receptor using structurally different antagonists.

Nine structurally dissimilar thromboxane antagonists (SQ 29548, ICI 185282, AH 23848, BM 13505 (Daltroban), BM 13177 (Sulotroban), SK&F 88046, L-636499, L-640035 and a Bayer compound SK&F 47821) were studied for activity as thromboxane A2 receptor antagonists. The assays used were inhibition of responses induced by the thromboxane mimetic, U46619, on human washed platelet aggregation, rabbit platelet aggregation, rabbit aortic strip contraction, anaesthetised guinea-pig bronchoconstriction, and a radio-labelled ligand (125I-PTA-OH) binding assay as a measure of affinity for the human platelet receptor. The results of the present study, with activities spanning at least four orders of magnitude along with statistically significant correlations (at least P less than 0.

Synthesis and biological activity of the four stereoisomers of 6-[4-[3-[[2-hydroxy-3-[4-[2- (cyclopropylmethoxy)ethyl]phenoxy]propyl]amino]-propionamido] phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone, a combined vasodilator and beta-adrenoceptor antagonist.

6-[4-[3-[[2-Hydroxy-3-[4-[2- (cyclopropylmethoxy)ethyl]phenoxy]propyl]amino]propionamido] phenyl]- 5-methyl-4,5-dihydro-3(2H)-pyridazinone (3) consists of a mixture of four stereoisomers, i.e., two racemates, as a consequence of the two asymmetric centers contained in the structure.

Design and synthesis of a series of combined vasodilator/beta-adrenoceptor antagonists based on 6-arylpyridazinones.

A series of new 6-[4-[[(aryloxy)acyl]amino]phenyl]-4,5-dihydropyridazinones have been synthesized and evaluated as combined vasodilator/beta-adrenoceptor antagonists and potential antihypertensive agents. Many of the early compounds displayed an unacceptably high level of intrinsic sympathomimetic activity (ISA) and a relatively short duration of action. Disubstitution in the 2,3-positions or in the 4-position of the aryloxy ring gave compounds with low ISA levels and, in some instances, improved duration of action.

SK & F 95018, a vasodilator/beta-adrenoceptor antagonist.

The pharmacological properties of a novel vasodilator/beta-adrenoceptor antagonist, SK & F 95018 6-[4-[3-(3-[4-(2-Cyclopropylmethoxyethyl)phenoxy]-2- hydroxypropylamino)propionamido]phenyl]-4,5-dihydro-5-met hylpyridazin- 3(2H)-one methanesulphonate] are described. SK & F 95018 lowered blood pressure and increased hindquarters blood flow in anaesthetised rats over the same dose range 1-5 mumol kg-1. Over a similar dose range SK & F 95018 inhibited isoprenaline-induced tachycardia in ganglion-blocked, anaesthetized cats.

The effects of compliance on measurement of hydraulic conductivity in microvessels.

A method for the measurement of compliance in mesenteric frog capillaries and rat venules is described briefly. The error introduced by capillary compliance in the measurement of hydraulic conductivity is then discussed in the light of these measurements and some of the recent literature on hydraulic conductivity are reassessed.