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L T Jespersen

Publications and source records attributed to L T Jespersen.

25 records · Page 2Linked to original sources

Studies on the effect of histamine in isolated human pulmonary arteries and veins.

The effect of histamine (0.01-200 microM) was studied in isolated human pulmonary vessels. Histamine induced concentration dependent contractions in both arteries and veins. In veins the maximal response to histamine was lower than in arteries. Histamine and 2-methyl-histamine had a dual action in both arteries and veins clearly demonstrated in vessels precontracted with potassium. In these vessels histamine and 2-methyl-histamine induced relaxation at low concentrations and contractions at high concentrations. Veins were more sensitive to the relaxant effect of histamine than arteries. Mepyramine eliminated the dual action of 2-methyl-histamine and histamine and unveiled a mepyramine resistant relaxation at the highest histamine concentrations used which was resistant to the effect of cimetidine and metiamide. The H2 receptor agonist dimaprit (10-400 microM) induced a slight relaxation in both arteries and veins that could be eliminated by metiamide (100 microM). The results show that histamine has a dual action in human pulmonary vessels which includes a contractile effect mediated via H1 receptors and a relaxant response partly mediated through H1 receptors and partly via unspecific mechanisms. However, an H2 mediated relaxant effect cannot be excluded.

Aged↗

Effects of two new Ca-entry blockers bepridil and nitrendipine on isolated vessels.

The effects of nitrendipine and bepridil were studied in isolated rings of human crural veins contracted by noradrenaline (NA) or potassium (K). Both drugs had a concentration dependent inhibitory effect on active tone and shifted the NA and K concentration-response curves to the right in a non-parallel manner and reduced the maximum contractile response. Both drugs had a more potent inhibitory effect on K than on NA-induced contractions. Nitrendipine was far more potent in inhibiting the K-induced contractions than bepridil while the drugs were equipotent in inhibiting NA-induced contractions. Human veins were less sensitive than rat aorta to the inhibitory effect of nitrendipine. In contrast to nitrendipine the effect of bepridil was gradual and slow in onset. The inhibitory effect of both drugs was strong and long-lasting and resistant to washout procedures. Both drugs effectively eliminated spontaneous mechanical activity and reduced K-induced contractions in rat portal veins. The results support that nitrendipine and bepridil are effective vasodilators in arteries as well as in veins. The main action of both nitrendipine and bepridil seems to be attributed to an inhibitory effect on cellular Ca-entry.

Adult↗

A novel principle for detection of systolic and diastolic blood pressure tested in man and rat with special reference to its applicability in rat studies.

A non-invasive procedure for the application of a photodetector method in rat studies to obtain both systolic and diastolic blood pressure measurements is described. The method has been tested against well-established procedures in rats and in human beings and has proved sufficiently fast and reliable for use in long-term studies. Regression analysis of simultaneously obtained invasive versus non-invasive measurements yielded correlation coefficients of 0.99 and 0.98 respectively. Comparison with the Korotkoff principle in human beings yielded correlation coefficients of 0.96 and 0.78 respectively.

Animals↗

Drinking water and drug dosage in rat studies.

Spontaneously hypertensive rats were treated with verapamil, hydralazine, indapamide or bepridil added to their drinking water. These substances had most different effects on the water consumption of the animals, displaying both positive and negative feed-back mechanisms. Furthermore there were considerable differences in stability of the drugs in solution. It is therefore concluded that continuous control of water intake and analysis of the stability of the drug is essential for the establishment of proper dose-response relationships.

Animals↗

Treatment with verapamil reduces blood pressure and tends to normalize vascular responsiveness and ion transport in the spontaneously hypertensive rat.

Spontaneously hypertensive rats (n = 7) were treated with verapamil in the drinking water (0.9 g/L) for a 5-month period. Blood pressure and heart weight in these animals were significantly lower than in a control group of rats (n = 7) receiving tap water. Aortic preparations from spontaneously hypertensive rats treated with verapamil showed less dependency on extracellular calcium in isometric tension studies than did aortae from control rats. Net uptake of 22Na and 45Ca in the presence of ouabain was significantly lower in verapamil-treated aortae than in aortae from control spontaneously hypertensive rats. The results indicate that treatment with verapamil is an effective antihypertensive regimen in spontaneously hypertensive rats and furthermore may tend to normalize vascular responsiveness and ion transport.

Animals↗

Effects of nifedipine on contractile responses to potassium, histamine, and 5-hydroxytryptamine in isolated human pulmonary vessels.

Isolated human pulmonary arteries and veins cut to ring preparations responded with maximum contractions to potassium (127 mM; K), histamine (90 microM), and 5-hydroxytryptamine (47 microM; 5-HT). Nifedipine (0.003-3 microM) had a concentration-dependent relaxant effect on contractions induced by K, histamine, or 5-HT. The magnitudes of the relaxant effect of nifedipine were equal in arteries and veins, except in the highest concentrations used, in which case the effect was more pronounced on K-induced contractions in veins than in arteries. The effect of nifedipine was less pronounced on contractions induced by histamine or 5-HT than on K-induced contractions, and was more pronounced on histamine- than on 5-HT-induced contractions. In Ca-free medium, the response to K was nearly abolished in both arteries and veins. When the Ca concentration was increased from 0 to 4 mM without nifedipine, the contractile response to K was completely restored, while in the presence of nifedipine the response to extracellular Ca was nearly abolished in both types of vessel. The results indicate that active tone induced by K in pulmonary vessels is dependent on Ca entry from the extracellular medium. Nifedipine has a relaxant effect on both arteries and veins. In both types of vessel contractions induced by histamine or 5-HT are more resistant to the effect of nifedipine than contractions mediated by depolarization.

Aged↗

Cardiac mass and peripheral vascular structure in hydralazine-treated spontaneously hypertensive rats.

We have examined the effect of antihypertensive treatment on heart weight and on structural and functional characteristics of isolated mesenteric resistance vessels (internal diameter 170-220 micron) in spontaneously hypertensive rats (SHR) and in Wistar-Kyoto rats (WKY). The SHR and WKY were treated with hydralazine from the age of 4 weeks and were examined at ages 12 to 14 weeks and 23 to 27 weeks. Treated SHR had a mean blood pressure as much as 29% below that of control WKY, which in turn was 25 to 40% less than that of control SHR. In 12- to 14-week-old rats the heart to body weight ratio (which in control SHR was 13% greater than of WKY) was unaffected by treatment. Thereafter, the heart to body weight ratio of treated SHR did not increase as much as usual. At both ages, the media thickness and contractile response of the resistance vessels of the SHR (which were, respectively, 37% and 30% greater than those of vessels of WKY) were unaffected by treatment. However, because treatment caused a small (8%) increase in the lumen diameter of the vessels of the SHR, treatment did cause small, but possibly physiologically important, decreases both in the media to lumen ratio (11%) and in the pressure against which these vessels would have been able to contract (10%). Treatment had little effect on the pharmacological characteristics of vessels of either SHR or WKY. The results suggest that the increased heart weight, media thickness, and contractile response in mesenteric resistance vessels of SHR up to ages 23 to 27 weeks are due primarily to factors other than increased pressure.

Aging↗