Long-term inhibition of NO synthase induces cardiac hypertrophy with a decrease in adrenergic innervation.

Data concerning the effect of NO on the function and structure of the heart are controversial. We have studied two main questions: (i) Does the heart muscle reflect the hypertension induced by long-term inhibition of NO synthase? (ii) Since the arginine-NO pathway is also operative in the autonomic nervous system, the second goal was to ascertain the possible changes of the adrenergic nervous system in the heart after long-term NO synthase inhibition. Wistar rats were administered L-NAME in drinking water (50 mg/kg bw/day) for 8 weeks. Systolic blood pressure and heart rate were monitored weekly. The heart/body weight ratio were determined at the end of experiment. The adrenergic nerve terminals visualized by histochemistry were counted according to Haug's point counting method. Blood pressure increased significantly in L-NAME-treated rats. No changes were found in the heart rate. Heart/body weight ratio increased markedly. Surprisingly, the density of adrenergic nerve terminals did not alter accordingly. The density of adrenergic nerve terminals in the left ventricle and septum decreased but no significant changes were found in the left atrium and the right ventricle. Hypertension due to NO deficiency induced cardiac hypertrophy that was characterized by a decline in the density of adrenergic innervation of the overloaded left ventricle and septum.

[The action of instilled physostigmine on the acetylcholine content of the bovine ciliary body (author's transl)]. / Action de la physostigmine instillée sur le taux d'acétylcholine du corps ciliaire des bovins.

The authors have compared the content of acetylcholine (ACh) of the two ciliary bodies (150 microgram of tissue) after the instillation of a stimulating dose of a 1% aqueous solution of physostigmine (10 applications of three drops at intervals of three minutes) into the conjunctival fornix of one eye. Kymographic measurements on guinea-pig ileum demonstrated an average elevation of the ACh content in the instilled ciliary bodies (0.48 microgram) against the controls (0.33 micron). The eyes were enucleated one hour after the last application.

[Action of physostigmine on the acetylcholine content of the bovine choroid (author's transl)]. / Action de la physostigmine sur le taux d'acétylcholine dans la choroïde des bovins.

The measurement of the acetylcholine (ACh) content of 12 choroids influenced by a 1% solution of physostigmine salicylate (10 applications of three drops at three minute intervals) into the conjunctival fornix of one eye demonstrated elevated average values for ACh content (0.87 microgram) compared with those for the control eye (0.75 microgram). The eyes were enucleated one hour after the last application.

[The action of instilled physostigmine on the acetylcholine content of the bovine retina]. / Action de la physostigmine instillée sur le taux d'acétylcholine dans la rétine des bovins.

Kymographic measurements of acetylcholine (ACh) in bovine retinal tissue carried out on guinea-pig ileum do not indicate a significant elevated concentration of ACh in the eye instilled with physostingmine salicylate (1% aqueous solution, 10 applications of three drops at intervals of 3 minutes). The eyes were enucleated one hour after the last application.

[Action of physostigmine on the acetylcholine level of the bovine iris]. / Action de la physostigmine sur le taux d'acétylcholine de l'iris des bovins.

The work discusses the measurement of acetylcholine (ACh) in the bovine iris in 150 mg of tissue on guinea-pig ileum. Prior to the extraction of ACh, a 1% solution of physostigmine salicylate (eserine) was instilled into the conjunctival sac ten times at a dose of three drops at intervals of three minutes (to a total of 15,000 micron g). The fellow eye of the same animal was left untreated and served as a control. One hour after the least instillation the animal was killed. The nine eserinised irides showed an average of 0.65 micron g ACh, and the nine controls an average of 0.47 micron g ACh (for 150 mg of tissue). The difference was statistically significant. In the discussion the authors admit that the amplitude of contraction of the guinea-pig ileum can be very little influenced by traces of eserine, possibly by binding effect. The form of eserine applied no longer influences the amplitude of the guinea-pig ileum contractions after an hour of in vivo action, and this is the same in considerably smaller doses where it is possible to prove its inactivation. Augmentation of the activity in the eserinised iris is adequate for the levels of acetylcholine. The more intensive action of eserine on the iris compared to that of pilocarpine is related to its greater binding power with the iris tissues.

[Acetylcholine in the bovine retina and the parasympathomimetic effect of pilocarpine]. / Acétylcholine de la rétine des bovins et effet parasympathicomimétique de la pilocarpine

Using titrations of acetylcholine (ACh) on guinea-pig ileum the authors have demonstrated that there is no significant statistical difference between the cholinergic activity of extracts of 150 mg of retinal tissue from pilocarpinised eyes (0.3 mug of ACh) and the activity of extracts from control eyes not subjected to pilocarpine (0.29 mug of ACh). The pilocarpine had been instilled into the bovine conjunctival sac at the rate of three drops of 3 p. 100 pilocarpine HCl ten times at intervals of three minutes. One hour after the last application the animals were killed and the eyes enucleated. The role of pilocarpine in the regulation of tissues in the posterior segment of the eye is discussed.

[Acetylcholine in the bovine choroid and the cholinergic effect of pilocarpine]. / Acétylcholine de la choroïde des bovins et effet cholinergique de la pilocarpine

In this study the authors have compared the cholinergic tone in a collection of bovine choroids after instillation of pilocarpine in the conjunctival fornix in one group using the opposite choroid from the same animal as a control. The tests for acetylcholine (ACh) were assayed on guinea-pig ileum. The choroidal nerves in the pilocarpinised eyes had an average level of 0,50 mug of ACh, the homologous choroidal nerves of the controls had an average level of 0,45 mug of standard ACh per 150 mg of tissue. The pilocarpine had been instilled in the conjunctival fornix as a 3 per cent aqueous solution of pilocarpine HCl, ten times three drops in intervals of three minutes. One hour after the last application the animals were sacrificed and the eyes enucleated. The authors discuss the clinica importance of the infiltration of pilocarpine into the choroid.

[Acetylcholine of bovine iris and cholinergic effects of pilocarpine]. / Acétylcholine de l'iris de bovins et effet cholinergique de la pilocarpine

The authors extracted acetylcholine (ACh) from bovine iris and carried out biological assay on guinea pig ileum. One of the pairs of irides were subjected in vivo for an hour to an aqueous solution of pilocarpine HCl 3 per cent, with the loading dose instilled in the conjunctival sac at the rate of ten times three drops in intervals of three minutes. The bio-assays of tissue extracts of pilocarpinised iris after one hour's action and the control studies present the following values: the amount of ACh in the pilocarpinised irides was 0,70 mug and in the controls it was 0,58 mug of ACh/150 mg of tissue. The remaining proportion of the elevated dose of pilocarpine applied to the iris tissue, one hour after the in vivo action, was comparable only to 1,5 mug of free pilocarpine or to a fifth of the ACh in the iris (0,12 mug). The results of these experiments demonstrate a complete decomposition of the pilocarpine as well as the existence of a certain limitation of elevation of the cholinergic tone in the iris tissues. The authors support data in the literature which indicates that pilocarpine raises the ACh levels. They do not attribute a fundamental importance to the raised loading dose of pilocarpine concerning the desired effect of a maximal elevation of cholinergic tone in order to achieve a favourable clinical effect in glaucoma.

[Acetylcholine in the bovine ciliary body and the cholinergic action of pilocarpine]. / Acétylcholine du corps ciliaire des bovins et action cholinergique de la pilocarpine

The authors have determined the acetylcholine (ACh) content in bovine ciliary bodies. One of the ciliary bodies was subjected in vivo to the influence of an aqueous solution of pilocarpine HCl 3 p. 100 which was instilled in the conjunctival cul-de-sac (ten times at a dose of three drops every three minutes). The contralateral ciliary body of the same animal served as a control for the ACh concentration. Enucleation was performed one hour after the last instillation. The average concentration of ACh estimated in 13 control ciliary bodies was 0,40 mug of ACh, and in 13 pilocarpinised eyes 0,50 mug of ACh (for 150 mg of tissue). The questions concerning the inactivation of pilocarpine and the source of augmentation of cholinergic tone in the pilocarpinised eyes have been discussed in previous communications.