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I S De la Lande

Publications and source records attributed to I S De la Lande.

At least 19 recordsLinked to original sources
PubMed1999

Tolerance induction by transdermal glyceryl trinitrate in rats.

Mechanisms of mild glyceryl trinitrate tolerance in rats (transdermal application; 15 mg/day/2 days) were examined in isolated aortic rings contracted with phenylephrine. Tolerance to glyceryl trinitrate was comparable in both endothelium-intact and -denuded vessels; the maximum relaxation decreased to 70-80% and the EC50 increased 3-4-fold. There was minimal cross-tolerance to acetylcholine (1.7-fold increase in EC50) and none to sodium nitroprusside. The results suggest that mild tolerance to glyceryl trinitrate in rats is mediated by mechanisms which are predominantly endothelium-independent and which produce little activation of the cellular mechanism responsible for cross-tolerance.

Acetylcholine↗
PubMed1999

Effects of guanylyl cyclase and protein kinase G inhibitors on vasodilatation in non-tolerant and tolerant bovine coronary arteries.

The effects in bovine coronary arteries of the soluble guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) were examined in order to establish the relative importance of the enzyme (a) in the vasodilator actions of glyceryl trinitrate and S-nitroso-N-acetylpenicillamine and (b) in induction of tolerance to these agents. ODQ strongly inhibited responses to both relaxants with IC50's of the order of 0.5 microM; in contrast, the protein kinase G inhibitor, 8-bromoguanosine-3',5'-monophosphorothioate (Rp-8-Br-cGMPS) had little effect on the responses. Tolerance after pre-incubation with glyceryl trinitrate (10 microM) was unaffected by co-pre-incubation with ODQ (1.0 microM), but similar experiments with S-nitroso-N-acetylpenicillamine were inconclusive because tolerance was associated with depressed contractile activity. It is concluded that in bovine coronary arteries soluble guanylyl cyclase is essential for vasorelaxation to both glyceryl trinitrate and S-nitroso-N-acetylpenicillamine but is unimportant for induction of tolerance to glyceryl trinitrate. Our results add weight to the hypothesis of impaired biotransformation rather than guanylyl cyclase desensitisation as the mechanism of in vitro nitrate tolerance.

Animals↗
PubMed1996

Heterogeneity of glyceryl trinitrate response in isolated bovine coronary arteries.

Factors determining heterogeneity of response to glyceryl trinitrate in coronary microvessels have been extensively documented in recent years, but determinants of heterogeneity between conduit and large resistance vessels are poorly understood. The current study has characterised heterogeneity to glyceryl trinitrate and other vasodilators in bovine isolated proximal (4.5 mm i.d.) and distal (0.5 mm i.d.) segments of left anterior descending artery. Compared with proximal segments, distal segments were less responsive to glyceryl trinitrate and sodium nitroprusside, equi-responsive to S-nitroso-N-acetylpenicillamine, and more responsive to isoprenaline. Heterogeneity to glyceryl trinitrate was unaffected by the presence of the thiols (cysteine or N-acetylcysteine, 100 microM). The results are interpreted as evidence that heterogeneity of vascular responsiveness to glyceryl trinitrate reflects impairment in the small artery of the cellular events which precede activation of the cyclic GMP pathway. An implication is that the impairment is not a consequence of limited thiol availability, and in this respect the cellular mechanism of heterogeneity differs from those proposed for the coronary microvasculature.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Lack of inhibition of glyceryl trinitrate by diphenyleneiodonium in bovine coronary artery.

Recent studies indicate that diphenyleneiodonium is a potent inhibitor of glyceryl trinitrate-induced relaxation in rat aorta precontracted with phenylephrine. We have explored the generality of this action in bovine coronary artery precontracted with the thromboxane A2 mimetic, 9,11-dideoxy-11 alpha, 9 alpha-epoxy-methano-prostaglandin F2 alpha (U46619). Diphenyleneiodonium 0.3 microM was without effect (endothelium absent) or caused mild potentiation (0.3 microM or 10 microM; endothelium present) of the relaxant response to gylceryl trinitrate. Lack of inhibition was not due to U46619, since inhibition was still prominent in rat aorta precontracted with this agent. It is concluded that diphenyleneiodonium distinguishes between cellular mechanisms mediating vasodilator responses to glyceryl trinitrate in rat aorta and bovine coronary artery.

Animals↗
PubMed1994

S-nitrosothiol modulation of tolerance to glyceryl trinitrate in bovine isolated coronary artery.

The aim of the study was to ascertain whether induction of tolerance to glyceryl trinitrate (GTN) was modified by nitrosothiols. Vasodilator responses to GTN and to two nitrosothiols, namely S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-N-acetylcaptopril (SNOCAP) were measured in bovine coronary artery rings constricted with the thromboxane mimetic agent U46619. Pre-exposure of vessels to SNAP (10 microM) for 1 h resulted in cross-tolerance to GTN comparable with tolerance induced by GTN (1.0 microM). Tolerance was increased after pre-exposure to both agents. SNAP alone in lower concentrations (0.01, 0.1 and 1.0 microM) did not produce cross tolerance to GTN, but in combination with GTN (1.0 microM) caused a small but significant decrease in tolerance to GTN. This attenuating effect of SNAP on GTN tolerance was reproduced by SNOCAP (0.01 microM). We conclude that the nitrosothiols exert a biphasic effect on induction of tolerance to GTN.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1988

Metabolism of exogenous noradrenaline in constricted and in distended rabbit ear arteries.

(1) The metabolism of extraluminal and of intraluminal 3H-noradrenaline (3H-NA; 0.18 mumol/l) was examined in arteries from reserpine-pretreated rabbits. The arteries were perfused in Ca medium (a) in the absence of prazosin to permit constriction to occur, (b) in the presence of prazosin, and (c) at a high intraluminal pressure (110 mm Hg; prazosin present) in order to distend the vessel. (2) The constrictor activity of the extraluminal NA was extremely weak, and antagonism by prazosin was not associated with a change in metabolite formation. The only change accompanying distension was a small (24%) increase in 3,4-dihydroxyphenylethylene glycol (DOPEG) formation. (3) The constrictor activity of intraluminal NA was much stronger than that of extraluminal NA. Antagonism of constriction by prazosin was accompanied by a 5-fold increase in DOPEG formation and a 2-fold increase in normetanephrine (NMN) formation. Distension resulted in a further 3-fold increase in DOPEG formation, but had little effect on NMN formation. (4) Since DOPEG is neuronal in origin, it is suggested that the changes in DOPEG formation in point 3 above reflect changes in the rate at which the intraluminal NA diffuses into the region of the sympathetic nerve terminals. In support of this suggestion, (a) distension was without effect when DOPEG formation was related to the vascular dimensions which determine rate of diffusion of NA, instead of to vascular mass, and (b) effects of constriction and distension on the rate of diffusion of intraluminal 14C-sorbitol across the artery wall paralleled their effects on DOPEG formation. (5) The effects of constriction on NMN formation in point 3 are attributed to diminished uptake2 (on which NMN formation depends) in the contracted smooth muscle, in association with tendencies for both NMN formation, and contractile activity, to be localized to the region of the vessel wall closest to the surface of entry of the NA. (6) Diffusion coefficients of 14C-sorbitol were estimated. The estimates indicate that (a) the changes in vascular dimensions are the prime determinants of rates of diffusion, (b) diffusivity is decreased when the vessel constricts, and (c) there may be bulk flow of the intraluminal medium into the vessel wall when it is distended by a high intraluminal pressure.

Animals↗
PubMed1970

The role of monoamine oxidase in the response of the isolated central artery of the rabbit ear to tyramine.

1. Monoamine oxidase activity was demonstrated histochemically throughout the media of the rabbit ear artery but not in the adventitia at its border with the media where the sympathetic nerve terminals are concentrated. Neither intensity nor distribution of enzyme activity was perceptibly altered up to 60 days after sympathetic denervation.2. Iproniazid and nialamide increased the sensitivity of the artery to intraluminal tyramine much more than that to extraluminal tyramine, so that the difference between the potencies for the two routes of administration became less marked.3. The results indicate that inactivation by monoamine oxidase in the media is a factor contributing to the relatively low potency of intraluminal tyramine on the artery.

Animals↗