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Biomedical subjects

D Regoli

Publications and source records attributed to D Regoli.

At least 379 records · Page 21Linked to original sources
PubMed1977

The role of prostaglandins in hypertension. I. The release of prostaglandins by aorta strips of renal, DOCA-salt, and spontaneously hypertensive rats.

The release of prostaglandin-like (PG-like) material by aorta strips of normotensive and hypertensive rats has been studied in vitro. When incubated in an oxygenated Krebs solution kept at 37 degrees C, aorta strips removed from 8- and 12-week-old spontaneously hypertensive (SH) rats generate 1.2-2.5 times more PG-like material than aorta strips from age-matched normotensive Wistar (NW) rats. The overproduction of PG-like material by aorta strips of SH rats did not precede the development of hypertension in SH rats. Aorta strips derived from renal and DOCA-salt hypertensive rats produced 1.5-3 times more PG-like material than aorta strips from NW rats. The production of PG-like material by aorta strips of renal and DOCA-salt hypertensive rats was largely reduced when hypertension was interrupted in these animals, thus suggesting that the alteration taking place in the arteries of hypertensive rats (namely increased production of PGs) during the development of hypertension was reversible. The production of PG-like material by aorta strips of hypertensive rats was inhibited by indomethacin. Analysis of the PG-like material by bioassays and thin-layer chromatography suggests the presence of PGE2 and PGE1. The possible involvement of these PGs in the pathogenesis of hypertension in rats is discussed.

Animals↗
PubMed1977

Effects of angiotensins and catecholamines on the transmembrane potential and isometric force of rattib isolated atria.

The action of angiotensin II (ATII), 1-des-Asp-ATII (Hepta-2-8), angiotensin I (ATI), 1-Sar,8-Gly-ATII and catecholamines on isometric force and transmembrane potential were studied in rabbit isolated atria, driven electrically. In some experiments two microelectrodes were implated to record simultaneously cjamges of intracellular electrical events in the left and in the right atrium: changes of tension were recorded isometrically. In other experiments changes of transmembrane potential were measured with floating microelectrodes. Norepinephrine and epinephrine increased tension, prolonged the plateau phase of the action potential (A.P.) in both atria, while facilitating conduction. ATII and 1-des-Asp-ATII showed similar effects on tension and greater changes on the electrical events of the left than on the right atrium, while ATI was more effective on the right than on the left atrium. 1-Sar, 8-Gly-ATII had no direct effect but prevented or reduced the action of ATII, 1-des-Asp-ATII and ATI, without influencing norepinephrine and epinephrine. All angiotensions except 1-Sar,8-Gly-ATII slightly prolonged the time of conduction. The results indicate that: a)angiotensins and catecholamines prolong the duration of the action potential and induce minor changes of potential overshoot in atrial fibers; b) ATII and 1-des-Asp-ATII act preferentially on the left and ATI on the right atrium; c) 1-Sar,8Gly-ATII inhibits secifically the effects of ATII and ATI in this preparation.

Action Potentials↗
PubMed1976

Characterization of angiotensin receptors in rabbit isolated atria.

Rabbit isolated left atria have been used to study the inotropic action of angiotensin II (ATII). The peptide is active at doses ranging from 1.0 x 10(-9) to 2.8 x 10(-6)M and its inotropic effect is not modified by sotalol, phentolamine, burimamide, and indomethacin. We therefore propose that this effect results from the stimulation of receptors specific for ATII. Dose-response curves of ATII obtained in presence of increasing concentrations of 8-Gly-ATII are gradually displaced to the right, but high doses of the antagonist depressed the maximum contractions caused by ATII. pA2 value for 8-Gly-ATII in this preparation is similar to those observed in vascular and intestinal smooth muscles. Order of potency of analogues of ATII (2-, 3- and 5-Ala-ATII), acting as full agonists, but with reduced affinity, is similar to that found in rabbit aorta strips. It is therefore proposed that receptors for ATII in rabbit isolated left atria are pharmacologically similar to those present in vascular smooth muscles. Positive inotropic effects of angiotensin I, undecapeptide (1-11), dodecapeptide (1-12) and tetradecapeptide (1-14) renin substrate are antagonized by 8-Gly-ATII in similar way as the effect of ATII. This suggests that the action of these peptides is mainly due to stimulation of receptors for ATII. The contribution of myocardial converting enzyme to the action of these peptides is discussed.

Angiotensin II↗
PubMed1975

Characterization of an angiotensin II-fluorescamine derivative.

The coupling of fluorescamine (4-phenylspiro[furan-2(3H), 1'-PHTHALAN]-3,3'dione) to angiotensin II to form a fluorescent derivative was studied. Complete reaction of the peptide below concentrations of 10- minus 4 M could be achieved with a fluorescamine concentration of 0-3 mg ml- minus 1 of acetone at pH 8-3, and the lowest concentration detectable by fluorescence spectroscopy was 100 pmol ml- minus 1. The derivative, as prepared did not react with ninhydrin, and no fluorescence was generated when fluorescamine was reacted with (1-Sar)-ATII. These data suggest that fluorescence is generated only through the coupling of fluorescamine to the N-terminal primary amine of ATII. The ATII-fluorescamine derivative has the same intrinsic activity on the contraction of rat colon (elevenfold loss of affinity), and on the release of fluorogenic corticosteroids from bovine adrenal cortical slices (sixfold loss of affinity) compared to ATII. Water-hydrolysed fluorescamine and Asp-fluorescamine did not contract rat colon preparations; the contractile response to ATII-fluorescamine was blocked by (8-Leu)-ATII, a specific ATII antagonist. These findings suggest that theATII fluorophore shares a common receptor site with the native octapeptide. The rate loss of biological activity of the ATII-fluorescamine derivative was appreciably lower than that observed for ATII. The present study suggests that the ATII-fluorescamine derivative can be substituted for radioactively-labelled ATII for use in a variety of applications.

Adrenal Cortex↗
PubMed1975

Application of drug receptor theories to the analysis of the myotropic effects of bradykinin.

Cat jejunum and terminal ileum, and rat stomach strip and rat uterus contract to bradykinin, while rat duodenum relaxes. Dose-response curves of classical hyperbolic shape are obtained in the first three preparations, but not in the others. The negative logs of the drug concentrations which give 50% of the maximal response. (pD2) Values were, respectively, 7.68 and 7.77 in the cat jejunum and terminal ileum, 6.78 in the rat stomach strip and 8.64 in the rat uterus in estrus. Theoretical dose-response curves, constructed by using experimental pD2 values in the equation of Clark, (General pharmacology. Verlag Van J. Springer, Berlin, 1937), are superimposed to experimental curves, obtained in the cat jejunum and terminal ileum, but not in the rat stomach strip. This comparison was not made in the rat uterus and duodenum. The myotropic effect of bradykinin appears to be a direct one in the cat jejunum, the terminal ileum and the rat stomach strip, because it is not affected by anticholinergics, antiadrenergics, antihistaminics and indomethacin. pD2 values and the slope of the dose-response curves of the rat uterus were reduced by indomethacin. The results indicate that cat jejunum and terminal ileum are sensitive and specific for bradykinin and appear to be the most reliable preparations for studies on the structure-activity relationships of this peptide.

Animals↗
PubMed1975

Role of the C-terminal group for the biological activities of angiotensin.

The C-terminal group of angiotensin II (ATii) , 1-Sar-ATii, and 1-beta-Asp-ATii was esterified to reduce degradation of the peptides and carboxypeptidases. Biological activity of esterified angiotensins was measured in vivo (rat blood pressure) and in vitro (rabbit aorta strip). Degradation in vitro by purified carboxypeptidase was estimated from the intensity of the phenylalanine spot on paper chromatography. Disposition of esterified angiotensins by rabbit aorta strips was studied with the oil immersion technique of Kalsner and Nickerson, Can. J. Physiol. Pharmacol. 46, 719-7308 (1968a). The results indicate that esterification of C-terminal group of ATii: (a) reduces the potency in vivo and to greater extent the affinity in vitro, (b) delays the onset of the contraction in vitro, (c) does not affect the intrinsic activity, (d) prolongs the time of relaxation of rabbit aorta strips in oil, (e) prevents the degradation by purified carboxypeptidase. It is proposed that C-terminal group of ATii contributes to affinity but not to instrinsic activity and facilitates the diffusion of the peptide to receptor sites. Esterification of this group prevents the degradation of the peptide by carboxypeptidases; accordingly, the duration of action in vivo is prolonged and the rate of relaxation of aortic strips in oil is reduced. When esterification of the C-terminal is combined with the replacement of Asp by beta-Asp in position 1, no relaxation of aortic strips occurs after oil immersion. This suggests that carboxypeptidases, and to a minor extent aminopeptidases, are responsible for the inactivation of angiotensin by rabbit aorta.

Aminopeptidases↗
PubMed1975

In vitro production of prostaglandins by isolated aorta strips of normotensive and hypertensive rats.

When suspended in oxygenated Krebs solution at 37 degrees C, strips derived from thoracic aortae of spontaneously hypertensive rats maintain their initial intrinsic tone and release prostaglandin-like material in the suspending medium, while similar preparations from normal Wistar rats relax progressively and produce significantly smaller amounts of prostaglandins. Indomethacin, a potent antagonist of prostaglandin synthesis, has two major effects: it favors the relaxation of both strips of hypertensive rats and of normal rats; and it inhibits the accumulation of prostaglandin-like material in the suspending medium, as evaluated with a specific and sensitive biological assay (rat stomach strip or chick rectum). Carotid and femoral arteries taken from the same animals show similar differences as the aorta strips, with regard to the production of prostaglandin-like material. The generation of prostaglandin is markedly decreased by the absence of O2, while it is unaffected by the absence of the extracellular Ca2+. It is proposed that the absence of relaxation of aorta strips taken from hypertensive, compared to normal rats, is due to increased intramural synthesis and release of prostaglandins.

Animals↗
PubMed1974

Release of prostaglandins from the rabbit perfused kidney: effects of vasoconstrictors.

1 The rat stomach strip was used to assay prostaglandin E(2)-like material released by a rabbit isolated kidney perfused with Krebs solution.2 Doses of noradrenaline and angiotensin II producing similar vasoconstrictor effects released equivalent amounts of prostaglandins from the kidney.3 8-Leu-angiotensin II, a specific inhibitor of the natural octapeptide, blocked the action of angiotensin II on perfusion pressure and the release of prostaglandins, while the action of noradrenaline on both parameters was unaffected.4 Indomethacin, a specific inhibitor of prostaglandin biosynthesis, blocked the effects of both vasoconstrictors on prostaglandin release while their action on perfusion pressure was significantly enhanced.5 In the kidney effluent, amounts of prostaglandin E(2)-like material increased linearly with the rise in perfusion pressure induced by increasing doses of angiotensin II. These results indicate that prostaglandin output from the isolated kidney follows the rise in perfusion pressure.

Angiotensin II↗
PubMed1973

Characterization of angiotensin receptors in vascular and intestinal smooth muscles.

1. A series of analogues of angiotensin II (AT(II)) has been used in the present experiments to characterize receptors for AT(II) in intestinal (rat stomach strip, rat colon) and vascular (rabbit aorta) smooth muscles. Two types of compounds have been chosen: (a) agonists with reduced potency, in which 4-Tyr, 6-His or 7-Pro had been substituted with L-Ala or with Gly and 1-amino-cyclopentane carboxylic acid (Acpc) and (b) competitive antagonists (8-Gly-AT(II), 8-Leu-AT(II)).2. Replacement of 4-Tyr, 6-His and 7-Pro with L-Ala decreases the potency, but does not influence the maximum effect of the analogue, while substitution of the same residue with Gly and Acpc reduces both potency and maximum effect.3. Compounds showing full size maximum responses were chosen to establish the following order of potency on the three preparations: AT(II)>4-Phe-AT(II)>7-Ala-AT(II)>6-Ala-AT(II)>4-Ala-AT(II).4. The four derivatives of AT(II) were completely inactive on tissues desensitized with AT(II). The responses to 5-hydroxytryptamine, acetylcholine and noradrenaline were not significantly modified, except for the rat colon.5. pA(2) values for the two competitive antagonists against AT(II) and 4-Phe-AT(II) were estimated in the three preparations by the use of the cascade superfusion technique. For comparison, pA(2) values were also estimated in rat stomach strips and rabbit aortas suspended in a normal organ bath, according to the method of Schild (1947). The similarities of the pA(2) values obtained in two series of experiments indicate that (a) the cascade superfusion technique is suitable for this type of study and (b) the receptor for AT(II) in the three tissues may be the same.6. It is suggested that receptors for AT(II) in intestinal and vascular smooth muscles may be the same, because (a) the order of potency of various agonists follows the same pattern, (b) the agonists are inactive on tissues desensitized with AT(II), (c) pA(2) values for competitive antagonists are similar in the three preparations.

Angiotensin II↗