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Biomedical subjects

A Bianchetti

Publications and source records attributed to A Bianchetti.

At least 127 records · Page 7Linked to original sources
PubMed1988

Arterial compliance and baroreceptor sensitivity after chronic treatment with indapamide.

Arterial compliance, assessed by the ratio of stroke volume to pulse pressure, and baroreceptor sensitivity (Oxford method), were determined in ten patients with essential hypertension, treated with placebo or indapamide (2.5 mg/day), in a cross-over, single blind study. After three months of therapy, mean arterial pressure was significantly reduced from 127 +/- 10 to 118 +/- 9 mmHg, (P less than 0.001), as was total peripheral vascular resistance (from 3017 +/- 561 to 2457 +/- 614 dyne/sec/cm-5/m2, P less than 0.001). Significant increases occurred in cardiac index (3.47 +/- 0.55 to 4.03 +/- 0.86 l/min/m2, P less than 0.01), baroreceptor sensitivity assessed with phenylephrine (from 11.69 +/- 7.9 to 15.0 +/- 9.1 msec/mmHg, P less than 0.01) or with nitroglycerine (from 4.77 +/- 1.6 to 7.11 +/- 2.7 msec/mmHg, P less than 0.01) and arterial compliance (from 1.27 +/- 0.42 to 1.55 +/- 0.57, P less than 0.01). A significant direct correlation was found between arterial compliance and baroreceptor sensitivity assessed during induced increase and reduction of BP, both during placebo (r = 0.88, P less than 0.001 and r = 0.77, P less than 0.01, respectively) and during active therapy (r = 0.94, P less than 0.001 and r = 0.92, P less than 0.001, respectively). These results support the conclusion that chronic treatment with indapamide enhances arterial compliances and reduces the heart load and blood vessel stress. The same effect could explain the enhancement of baroreceptor sensitivity promoted by the drug.

Adult↗
PubMed1986

Dissociation of morphine withdrawal diarrhea and jumping in mice by the peripherally selective opioid antagonist SR 58002 C.

Mice were rendered physically dependent by repeated administration of morphine, 25 mg/kg s.c., 5 times daily for 4 days, and on the 5th day, 2 h after the last morphine dose, they were challenged with a s.c. injection of either naloxone, 25 mg/kg, or the peripherally selective opioid antagonist SR 58002 C (N-methyl levallorphan mesilate), 75 mg/kg. Naloxone provoked jumping and diarrhea in all the animals; mice challenged with SR 58002 C presented no significant jumping but a high frequency of withdrawal diarrhea. When naloxone, 12 mg/kg, or SR 58002 C, 50 mg/kg, were given s.c. in combination with repeated morphine as above, mice which had received naloxone with morphine presented virtually no diarrhea or jumping upon naloxone challenge; those repeatedly treated with morphine plus SR 58002 C were substantially protected from naloxone-precipitated diarrhea, but not jumping. These results further support the remarkable selectivity for peripheral opioid receptors of SR 58002 C, even after repeated high-dose treatment, and are strongly consistent with the primary role of a local intestinal mechanism in the development and expression of opioid withdrawal diarrhea in mice. The in vivo dissociation of central and peripheral components of dependence on morphine is illustrated, apparently for the first time.

Animals↗
PubMed1986

Inhibition of dimaprit- and pentagastrin-induced gastric acid secretion in cats by the new histamine H2 antagonist, CM 57755.

The antisecretory effects of CM 57755, a new histamine-H2 receptor antagonist, have been compared with those of cimetidine on gastric acid secretion induced by intravenous infusions of dimaprit or pentagastrin into conscious cats with chronically implanted gastric fistulae. Intravenous infusion of CM 57755 induced a parallel shift to the right of the dimaprit dose-response curve. The potency of CM 57755 was comparable with that of cimetidine as shown by similar doses causing a 5-fold displacement to the right of the dimaprit dose-response curve (4.9 mumol kg-1 h-1 for CM 57755 and 4.7 mumol kg-1 h-1 for cimetidine). Unlike that with dimaprit, the acid secretion stimulated by increasing doses of pentagastrin was inhibited by CM 57755 with depression of the maximal effect, indicating non-competitive antagonism. In a second series of experiments the time course of the anti-secretory action of intragastrically administered CM 57755 was studied from the gastric acid secretion induced by constant infusion of dimaprit. At equieffective doses, CM 57755 caused more sustained inhibition than cimetidine.

Animals↗
PubMed1985

Relative affinities of the quaternary narcotic antagonist, N-methyl levallorphan (SR 58002), for different types of opioid receptors.

The relative affinities for different subtypes of opioid receptors (mu, kappa and delta) of the peripheral narcotic antagonist N-methyl levallorphan (SR 58002) have been studied in two in vitro smooth muscle systems (guinea-pig ileum and rabbit vas deferens) and by binding studies (guinea-pig brain and cerebellum membranes) using selective tritiated ligands. All the evidence obtained indicates that SR 58002 is a pure antagonist with relative affinity for mu receptors vs kappa and delta superior to that of the parent tertiary compound, levallorphan.

Animals↗
PubMed1984

In vivo and in vitro effects of CM 57755, a new gastric antisecretory agent acting on histamine H2 receptors.

The pharmacological activity of CM 57755, a new gastric antisecretory compound of the anti-H2 type, was studied in certain in vivo and in vitro preparations. In stomach-lumen perfused rats it proved to be, on a molar basis, half as active as cimetidine and 1/13 as active as ranitidine in inhibiting histamine-induced gastric acid secretion. On the other hand, CM 57755 administered to conscious gastric-fistula cats, either i.v. or intragastrically, depressed the hypersecretory plateau evoked by constant infusion of dimaprit with a potency comparable to that of cimetidine. In this preparation, the inhibition at equieffective doses of antagonists was more sustained for CM 57755 than for cimetidine and ranitidine. Applied to isolated guinea-pig right atria and gastric mucosa, CM 57755 competitively antagonized histamine effects (respective pA2's: 5.4 and 5.9) but was less potent than expected from its in vivo antisecretory activity. Bioavailability and/or biotransformation are the factors most likely to account for the differences observed between species, and between in vivo and in vitro studies for this long-acting antisecretory agent.

Animals↗
PubMed1983

Effect of indapamide on the baroreceptor reflex in essential hypertension.

The effect of chronic treatment with indapamide on blood pressure (BP), baroreceptor sensitivity (BRS) and vascular reactivity (VR) were investigated in 10 patients with essential hypertension. After 3 months of therapy with indapamide 2.5 mg/d the mean arterial pressure (MAP) had decreased from 135 +/- 6 to 112 +/- 2 mmHg (p less than 0.001); the heart rate (HR) had not changed, VR had decreased from 6.1 +/- 1.2 to 4.8 +/- 1.8 (pg . min . kg)-1 (p less than 0.05), and BRS had increased from 8.3 +/- 3.7 to 12.2 +/- 5.3 ms/mmHg (p less than 0.005), with a leftshift of the relationship between BP and heart period. An inverse correlation was found between the pre-treatment systolic blood pressure and the change in baroreceptor sensitivity after indapamide (r = 0.59; p less than 0.05). In conclusion, chronic treatment with indapamide enhances BRS and resets the reflex. The resetting may account for the lack of tachycardia at rest observed after treatment with indapamide. The mechanism by which indapamide interferes with the baroreceptor reflex requires further investigations.

Adult↗
PubMed1983

Quaternary derivatives of narcotic antagonists: stereochemical requirements at the chiral nitrogen for in vitro and in vivo activity.

We have studied three pairs of diastereoisomers of quaternary narcotic antagonists and their parent tertiary amines, levallorphan, nalorphine and naloxone, to see how configuration about the chiral nitrogen affects in vitro and in vivo activity. In each series only the diastereoisomer obtained by methylation of the N-allyl substituted tertiary amine (N-methyl diast.) was potent in displacing 3H-naltrexone from rat brain membranes (Ki 10(-8) - 10(-7)M) and as pure morphine antagonist in the guinea-pig ileum (Ki 10(-8)-10(-7)M). Conversely, diastereoisomers obtained by reacting N-methyl substituted tertiary amines with allyl halide (N-allyl diast.) did not displace 3H-naltrexone, up to 10(-6)M, and had negligible antagonist activity and slight agonist action in the guinea-pig ileum. In vivo findings (charcoal meal transit test in mice) were generally consistent with those in vitro. Thus only the N-methyl but not the N-allyl diast. inhibited morphine constipation and behaved as pure antagonists.

Animals↗
PubMed1983

Levallorphan methyl iodide (SR 58002), a potent narcotic antagonist with peripheral selectivity superior to that of other quaternary compounds.

The peripheral selectivity of the newer quaternary narcotic antagonist levallorphan methyl iodide (SR 58002) was found superior in mice to those of the previously available compounds N-allyl levallorphan (CM 32191), N-methyl nalorphine (MNph) and N-methyl naloxone (MNx). SR 58002 and MNph were the most potent (ID50, mg/kg s.c., 3.6 and 3.7) in preventing constipation by s.c. morphine (charcoal meal). Antinociception (hot-plate) of s.c. morphine was completely prevented by MNx, MNph and CM 32191 (ID50, mg/kg s.c., 1.6, 8.6 and 15.2) but only partially antagonized by 30 mg/kg s.c. SR 58002. Constipation elicited centrally by intracerebroventricular (i.c.v.) morphine was prevented by either s.c. MNx or MNph but not by SR 58002 or CM 32191, up to 60 mg/kg.

Animals↗
PubMed1983

Baroreflex function after therapy withdrawal in patients with essential hypertension.

1. Baroreceptor sensitivity and vascular reactivity to noradrenaline were assessed in patients with essential hypertension chronically treated with diuretics during treatment and 6-8 weeks after its withdrawal. 2. Stopping diuretics was followed by an increase in mean arterial blood pressure and vascular reactivity, while baroreceptor sensitivity decreased. 3. Baroreceptor sensitivity during treatment correlated directly with the time during which patients remained normotensive after stopping diuretics. 4. An inverse correlation was found between vascular reactivity and baroreceptor sensitivity after diuretic withdrawal and between the patients' age and baroreceptor sensitivity during diuretic therapy. 5. We conclude that the impairment of baroreceptor sensitivity after stopping diuretic therapy could result in an enhanced vascular response to noradrenaline, and a sensitive baroreflex could contribute to the control of blood pressure during diuretic treatment and buffers the return of high blood pressure when diuretics are stopped.

Adult↗