Browsing by Author "FOURNIER, A"

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    AGE AND CASTRATION MODULATE THE INHIBITORY-ACTION OF NEUROPEPTIDE-Y ON NEUROTRANSMISSION IN THE RAT VAS-DEFERENS
    (1991) BITRAN, M; TORRES, G; FOURNIER, A; STPIERRE, S; HUIDOBROTORO, JP
    The potency of neuropeptide Y (NPY) to inhibit the electrically induced contractions of the epididymal half of the vas deferens diminishes markedly with age, being at least 20 times lower in the adult than in the 26-day-old rat. Castration sensitizes the epididymal segment to NPY in a testosterone-reversible manner. [Pro34]NPY was 3 times less potent than NPY in prepubertal rats and inactive in castrated adults, while NPY-(13-36) had no effect in either group. In the prostatic half, NPY and its analogs were active in rats from all ages studied; the order of potency being NPY > [Pro34]NPY > NPY-(13-36). The sensitivity of the prostatic segment from adult rats to NPY was unchanged by castration or testosterone replacement therapy. The NPY content of the ductus increases during development being higher in,the prostatic than in the epididymal half at all ages studied. Castration decreases the peptide content in the two segments and the effect is prevented by testosterone administration. The present investigation demonstrated that the effect of NPY on vas deferens neurotransmission is subject to regulation by sex steroids, which affects differently the response of the two segments of the ductus.
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    AGING DIFFERENTIALLY MODIFIES ARTERIAL SENSITIVITY TO ENDOTHELIN-1 AND 5-HYDROXYTRYPTAMINE - STUDIES IN DOG CORONARY-ARTERIES AND RAT ARTERIAL MESENTERIC BED
    (1994) DONOSO, MV; FOURNIER, A; PESCHKE, H; FAUNDEZ, H; DOMENECH, R; HUIDOBROTORO, JP
    The influence of age on vascular reactivity to endothelin-1 (ET-1) and 5-hydroxytryptamine (5-HT) was studied in coronary artery rings from dogs of 9 years of age or younger, and dogs older than 9 years. ET-1 caused concentration-dependent contractions that developed about 100% of the 70 mM KCl-induced tension in the younger dogs; those from older dogs did not generate more than 20%. In contrast, 5-HT developed only about 20% of the KCl-induced tension in rings from young dogs, whereas in the older animals, it developed up to 120% of the KCl tension. No significant difference in the tension developed by 70 mM KCl was noted between both groups of dogs. Mechanical denudation of the endothelial cell layer caused a modest, yet significant, leftward shift of the ET-1 and 5-HT concentration-response curves only in the younger dogs. N omega-Nitro-L-arginine (15 mu M) shifted the ET-1 concentration-response curves to the left in rings from both groups of dogs. Rings precontracted with 20 mM KCl relaxed in a concentration-dependent fashion with acetylcholine; its sensitivity was about threefold less in the older group of dogs. To validate the changes in Vascular reactivity with age, a parallel study was performed perfusing the arterial mesenteric bed of rats of 3, 7, and 30 weeks of age. In this experimental model, the efficacy of ET-1 significantly decreased with age and that of 5-HT was significantly increased. The vasomotor reactivity of noradrenaline was modestly affected by aging, whereas the acetylcholine-induced vasorelaxation was significantly reduced with age.
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    ENDOTHELIN REDUCES MICROVASCULAR BLOOD-FLOW BY ACTING ON ARTERIOLES AND VENULES OF THE HAMSTER-CHEEK POUCH
    (1990) BORIC, MP; DONOSO, V; FOURNIER, A; STPIERRE, S; HUIDOBROTORO, JP
    Superfusion of the cheek pouch with 0.1-10 nM endothelin (E) produced a concentration-related reduction in the clearance of 22Na+ used as an indicator of microvascular plasma flow. The median effective concentration was about 2 nM. The time course of E action was also concentration related. Superfusion with 10 nM E for 10 min caused a greater than 80% reduction in 22Na+ clearance; the rate at which the action of E started was significantly faster than the rate at which its action ended. Recovery did not exceed 70% even though the tissue was superfused with drug-free buffer for 90 min. The E-induced reduction in 22Na+ clearance was associated with vasoconstriction, as determined by intravital microscopy. Arterioles by 4th branching order were more sensitive to E action than arterioles of 1st or 2nd order; however, the constriction lasted considerably longer in the latter vessels. E-induced venular constriction followed a pattern analogous to that of arterioles of the same category, with the exception that the finer venules responded the least. Pretreatment of the cheek pouch with 300 nM nifedipine diminished but did not abolish the 1 nM E-induced reduction in 22Na+ clearance, and the recovery of clerance upon E washout was not accelerated by nifedipine.
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    INVOLVEMENT OF ET(A) RECEPTORS IN THE FACILITATION BY ENDOTHELIN-1 OF NONADRENERGIC NONCHOLINERGIC TRANSMISSION IN THE RAT URINARY-BLADDER
    (1994) DONOSO, MV; SALAS, C; SEPULVEDA, G; LEWIN, J; FOURNIER, A; HUIDOBROTORO, JP
    1 Endothelin-l (ET-1; 3-10nM) raised the tone of rat bladders bathed in buffer containing atropine (1 mu M) plus guanethidine (3.4 mu M). In addition, ET-1 potentiated, in a concentration-dependent fashion (1-10nM), the contractions evoked by both transmural nerve stimulation and applications of exogenous adenosine 5'-triphosphate (ATP). 2 The threshold concentration of ET-1 required to facilitate non-adrenergic non-cholinergic (NANC) transmission and potentiate ATP-induced contractions, was about 10 fold lower than that required to increase the bladder tone (3nM). 3 The ET-l-induced increase in basal tension reached its maximal effect within 60-90s. In contrast, the 7.8 mu M ATP-induced contractions increased by 50% within the first minute following incubation with 10nM ET-1 but required about 5 min to develop the maximal effect. 4 The ET-l-induced potentiation of NANC or ATP responses was long-lasting and persisted in spite of extensive washing. The recovery of the bladder excitability depended on the concentration of ET-1. Following the application of 3nm ET-1, recovery required 30 min; applications of 10nM ET-1 required at least 60 min for full recovery. 5 The ET-1-induced potentiation of responses was selective for ATP and related structural analogues. ET-1 did not modify the contractions induced by acetylcholine, 5-hydroxytryptamine, prostaglandin F-2 alpha or bradykinin. 6 The potency of ET-2 was similar to that of ET-1. ET-3 and ET-C-terminal hexapeptide were inactive up to 100M. Sarafotoxin S6b was 2 to 3 fold less potent than ET-1 whereas sarafotoxin S6c (100nM) was inactive. AGETB-9 and AGETB-89, two ET(B) receptor agonists, were also inactive (up to 100nM). 7 Removal of one or both disulphide bonds in ET-1 and tryptophan-21 formylation of ET-1, resulted in inactive peptides (up to 100nM). 8 The ET-1 receptor antagonists, BE-18257B and FR139317, blocked both the ET-1-induced rise in tone and the potentiation of ATP responses in a concentration-dependent fashion. FR139317 was at least 30 fold more potent than BE-18257B. Both antagonists blocked at lower concentrations the ET-1 increase in bladder tone as compared to the ATP potentiation. The antagonism was slowly reversible. 9 Results are consistent with the presence of ET(A) receptors in the rat bladder, which mediate both actions of ET-1. The interaction of ET-1 with purinergic mechanisms is discussed.
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    PHARMACOLOGICAL CHARACTERIZATION OF CGRP1-RECEPTOR SUBTYPE IN THE VASCULAR SYSTEM OF THE RAT - STUDIES WITH HCGRP FRAGMENTS AND ANALOGS
    (1990) DONOSO, MV; FOURNIER, A; STPIERRE, S; HUIDOBROTORO, JP
    In order to examine whether the truncated fragments of hCGRP, hCGRP(8-37) or hCGRP(12-37), behave as competitive CGRP receptor antagonists in the vascular system of the rat, systemic blood pressure was continually monitored in pentobarbital-anesthetized Sprague-Dawley rats. The IV administration of 7.9-527 pmol hCGRP/rat caused dose-related reductions in mean arterial blood pressure that lasted, depending on the dose, about 3-10 min. In contrast, hCRRP fragments 8-37 or 12-37 proved inactive up to 60,000 pmol/rat. Pretreatment with either 10 or 30 nmol hCGRP(8-37) or 20 or 90 nmol hCGRP(12-37)/rat reduced the magnitude of the CGRP-induced hypotensive responses caused by 79 pmol hCRGP/rat; pretreatment with 10 nmol of the hCRGP fragments displaced about 3-fold the hCRGP as well as the [Cys(ACM)2.7]hCGRP dose-response curve to the right in a parallel fashion. The specificity of hCGRP(8-37) as a CGRP receptor antagonist was documented by the finding that it did not antagonize the hypotensive responses induced with bradykinin, histamine or substance P.