Per J. Nielsen

Immersion versus contact technique in the measurement of axial length by ultrasound

Abstract The axial length was measured by A‐scan in 60 cataractous patients using a non‐contact (immersion) and a contact technique. The mean axial length was found to be 23.49 mm with the immersion technique and 23.35 mm with the contact technique, using the same Sonometrics transducer probe. The difference of 0.14 mm (± 0.19) was significant at the 0.01 level. The difference should be taken into account when evaluating the accuracy of IOL calculation, and may call for different empirical corrections of the axial length with different ultrasonic equipment.

Role of the endothelium in acetylcholine-induced relaxation and spontaneous tone of bovine isolated retinal small arteries

Acetylcholine induced a variable concentration-dependent relaxation of bovine isolated retinal small arteries contracted with PGF2 alpha. The acetylcholine-mediated relaxation was linearly related to the sodium nitroprusside-induced relaxation, suggesting that the endothelium is well preserved in the vessels and that the variable effect of acetylcholine is due to variations in the soluble guanylate-cyclase enzyme activity in the smooth muscle. The vessels became desensitized to acetylcholine by repeated exposures. L-arginine and indomethacin did not abolish the desensitization. The vessels also became desensitized to the direct smooth muscle relaxing effect of sodium nitroprusside, indicating that desensitization to the endothelium-dependent relaxation by acetylcholine is related primarily to the vascular smooth muscle cells. Atropine, methylene blue and removal of endothelium abolished the acetylcholine-induced relaxation completely, whereas indomethacin had no inhibitory action on the acetylcholine-induced relaxation, suggesting that acetylcholine mediates release of EDRF (nitric oxide: NO) through stimulation of muscarinic receptors. Methylene blue contracted endothelium intact retinal arteries but a spontaneous tone was not present in endothelial denuded arteries. This may indicate a basal release of both a contractile factor, e.g. endothelin, and a relaxing factor. NO, form the retinal endothelium. The results demonstrate that endothelial-derived factors may participate in normal as well as pathophysiological regulation of retinal vascular smooth muscle tone.

Contractile and relaxing effects of arachidonic acid derivatives on isolated bovine retinal resistance arteries

The reactivity of isolated ring segments (i.d. ca. 200 microns) of calf retinal resistance arteries to arachidonic acid derivatives were studied in vitro. Prostaglandin F2 alpha (PGF2 alpha) prostaglandin E2 (PGE2), and a thromboxane A2 analogue, 9,11-dideoxy-9 alpha,11 alpha-epoxymethane-prostaglandin F2 alpha, (TX2 alpha), induced a concentration dependent contraction with the order of potency: Tx2 alpha greater than PGE2 greater than PGF2 alpha with pD2-values (-log[EC50(M)]) of 6.88, 6.19 and 5.20, respectively. The maximal active tension development of the vessels induced by Tx2 alpha, PGE2 and PGF2 alpha, were 1.57 N m(-1), 1.05 N m(-1) and 1.19 N m(-1), corresponding to 94%, 57% and 67% of Emax, respectively. The active pressure development, and estimate of the maximum pressure which the vessels may be able to contract against in vivo, was 18 kPa, 12 kPa and 14 kPa (138, 89 and 110 mmHg) for Tx2 alpha, PGE2 and PGF2 alpha, respectively. Prostaglandin I2 (prostacyclin, PGI2) induced a concentration-dependent relaxation of retinal resistance arteries precontracted with 10(-5) M PGF2 alpha. The maximal relaxation induced by PGI2 amounted to 65% of the control vessel response induced by PGF2 alpha (1.27 N m(-1] with a -log[EC50(M)] value of 6.51. The results indicate that arachidonic acid derivatives are potent and effective agents capable of regulating bovine retinal resistance artery smooth muscle tension in vitro.

Active wall tension — Length curve and morphology of isolated bovine retinal small arteries: Important feature for pharmacodynamic studies

The active and passive wall tension--internal circumference (diameter) relations of isolated ring segments of bovine retinal small arteries (i.d. ca. 200 microns) were studied in vitro using an isometric myograph. The active tension of the vessels (when fully activated with 10(-5) M 5-HT and 10(-5) M PGF2 alpha in high K(+)-saline) reached a maximum (1.2 N m-1) at an internal circumference, L0, where the passive tension (measured in Ca2(+)-free solution) were 0.89 N m-1. Below and above L0 the active tension fell linearly, the zero tension intercepts being 0.48 L0 and 1.61 L0. The passive wall tension rose exponentially as a function of the internal circumference (diameter) and was 43 times higher at 1.4 L0 than at L0. A small transient spontaneous contraction was observed after rapid stretch of the arteries. Papaverine and Ca2(+)-free solution did not change the wall tension of vessels stretched to L0, indicating absence of stable spontaneous myogenic tone in the vessels. Histological examination showed that the retinal artery media on average had three smooth muscle cell layers which in total were 12 microns thick. The media/lumen ratio was 7%. Smooth muscle cell volume was 1228 micron3, constituting about 72% of the media volume. The active wall tension--internal circumference relation and morphology of bovine retinal small arteries is generally equal to that of arteries of similar size from other species, but active force generation of the retinal vascular smooth muscle cells is considerably lower.

Adrenergic responses in isolated bovine retinal resistance arteries

SummaryThe reactivity of bovine retinal resistance arteries (i.d. ca. 200 μm) to selective alpha1-, beta- and combined alpha- and beta-adrenoceptor stimulation was studiedin vitro using phenylephrine, isoproterenol and norepinephrine, respectively. The results indicate that only functional alpha1-adrenoceptors, possibly in low numbers, are present in these vessels.

Calcium antagonist-induced relaxation of the prostaglandin-F2α response of isolated calf retinal resistance arteries

The relaxing effect of nitrendipine and D600 on isolated ring segments of calf retinal resistance arteries (i.d. ca. 200 microns) contracted with prostaglandin-F2 alpha (PGF2 alpha) or high potassium solution was studied. The vessel response to both PGF2 alpha and potassium stimulation was dependent on extracellular calcium. Removal of extracellular calcium reduced the vessel response to PGF2 alpha and potassium by 85% and 98%, respectively (P less than 0.01). Both calcium antagonists induced a concentration dependent relaxation of PGF2 alpha pre-contracted vessels with = -log[IC50(M)]-values of 8.01 and 7.13 for nitrendipine and D600 (P less than 0.05), respectively. The calcium antagonists were equieffective in relaxing the vessels amounting to 33% for nitrendipine at 10(-6) M and 37% for D600 at 10(-5) M. Further analysis of the data revealed that the nitrendipine induced relaxation of the PGF2 alpha response was linearly correlated with the internal lumen diameter of the vessels. No correlation was found for the D600 induced relaxation. At the highest concentrations of nitrendipine, 10(-6) M, and D600, 10(-5) M, the potassium induced response was reduced by 94 and 75%, respectively. The results show that calcium antagonists only partially relax retinal resistance arteries contracted with PGF2 alpha although the vessels are dependent on extracellular calcium for active force generation. Calcium must therefore be activated by PGF2 alpha through other pathways than those blocked by calcium antagonists.

The level of spontaneous myogenic tone in isolated human posterior ciliary arteries decreases with age.

The spontaneous myogenic activity of rings of human posterior ciliary arteries was studied in vitro. All arteries from six patients had an intrinsic myogenic tone, which was dependent on extracellular calcium and inversely correlated with age. The myogenic tone was stable without rhythmic variations, except in one artery. The level of spontaneous myogenic tone was higher in vessels where the endothelium was removed than in normal arteries. Acetylcholine induced a complete and concentration dependent relaxation of endothelium-intact but not endothelium-denuded arteries. Indomethacin induced a small concentration dependent contraction of the arteries. Methylene blue did also contract the arteries concentration dependently. The experiments indicate that the myogenic tone of human posterior ciliary arteries is regulated by prostaglandin formation (prostacyclin?) as well as release of endothelium-derived relaxing factor in the arteries. The results indicate that the blood flow regulatory capacity of these arteries may be endangered by aging and endothelial damage, which could increase the probability of developing, e.g. ischemic damage of the optic nerve head.

Angiotensin II does not contract bovine retinal resistance arteries in vitro

The effect of angiotensin II was studied in vitro on ring segments of bovine retinal resistance arteries (i.d. 126-271 microns) and posterior ciliary arteries (i.d. 207-1153 microns). Although the retinal resistance arteries were responsive to 5-hydroxytryptamine, prostaglandin F2 alpha, and changes in extracellular K(+)-concentration, they did not, in contrast to the posterior ciliary arteries, contract to cumulative or single doses of angiotensin II. In the latter arteries, angiotensin II induced a small concentration dependent contraction, 5% of maximal 125 mM K(+)-induced response, with a pD2-value of 9.3. The single addition of 10(-6) M angiotensin II increased the maximal vessel response of the posterior ciliary arteries three times to angiotensin II. Tachyphylaxis was pronounced in the posterior ciliary arteries, in which the response to angiotensin II could not be repeated. Indomethacin (10(-5) M), methylene blue (3 x 10(-6) M), or removal of endothelium did not make the retinal resistance arteries responsive to angiotensin II. Retinal arteries precontracted with 30 mM potassium did not respond to angiotensin II. Angiotensin II did not potentiate the 5-hydroxytryptamine- and noradrenaline concentration-response characteristics of both retinal resistance and posterior ciliary arteries. Although angiotensin II-receptors have been detected in bovine retinal vascular smooth muscle using radioligand-binding technique, the present results suggest that these receptors are non-functional in respect to regulation of retinal resistance artery tone.

Beta-adrenergic receptors regulating vascular smooth muscle tone are only localized to the intraocular segment of the long posterior ciliary artery in bovine eye*

Beta-adrenergic drugs are important drugs in glaucoma treatment. Their exact mechanism of action is not yet fully understood but a decreased perfusion pressure in the ciliary body due to blockade of vasodilatory beta-adrenoceptors is thought to participate in the reduction of intraocular pressure. This study investigates the vasodilator action of beta adrenergic-agents in intra- and extraocular arteries from bovine and human eyes. Ring segments of retinal, choroidal, intraocular segment of long posterior ciliary artery, and segments of extraocular posterior ciliary arteries from bovine eyes and short posterior ciliary arteries from freshly enucleated human eyes were mounted on an isometric myograph and their reactivity to beta-adrenergic drugs were studied. Of all vessel types examined only the intraocular segment of long posterior ciliary artery precontracted with prostaglandin F2 alpha responded to 1-isoprenaline (1 nM-1 microM) with a graded concentration-dependent relaxation (32 +/- 7%, n = 10) and a pD2 of 7.5 +/- 0.2 concentrations of 1-isoprenaline greater than 1 microM induced contractions which were antagonized by a combined blockade of alpha1- and alpha2-adrenoceptors. Salbutamol (selective beta2-agonist) induced relaxations of similar magnitude as that of 1-isoprenaline but the sensitivity of the intraocular segment of long posterior ciliary arteries to salbutamol was 312 times less than that to 1-isoprenaline, pD2 7.2 +/- 0.2 and 4.4 +/- 0.1 (n = 6), respectively, whereas dobutamine (selective beta 1-agonist) had no effect between 1 nM and 10 microM. Betaxolol (selective beta 1-antagonist) and 1CI 115811 (selective beta 2-antagonist) competitively antagonized isoprenaline-induced relaxations giving pKB-values of 5.9 +/- 0.1 (n = 11) and 8.5 +/- 0.1 (n = 6), respectively. The slope of the Schild-plots were equal to unity. Human posterior ciliary arteries with spontaneous tone or tone induced by 10 microM PGF2 alpha did not react to isoprenaline (1 nM-10 microM). The bovine intraocular segment of long posterior ciliary arteries contracted to 1-noradrenaline without alpha-adrenoceptor blockade and addition of propranolol or cocaine did not change the concentration-response curve. 1-Phenylephrine and B-HT933 induced both potent and strong contractions indicating the presence of both alpha 1- and alpha 2-adrenoceptors in these arteries. Although beta-adrenoceptors have been identified in various parts of the ocular circulation by radio-ligand binding techniques our data show that beta-adrenoceptors linked to regulation of vascular tone are only found in intraocular branches of the intraocular segment of long posterior ciliary artery in bovine eyes.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcitonin gene-related peptide is a potent vasodilator of bovine retinal arteries in vitro.

Calcitonin gene-related peptide (CGRP) invariably induced a slow acting but potent relaxation of bovine retinal small arteries contracted with PGF2 alpha. Maximal relaxation obtained was 93% and 96% with a pD2-value of 8.97 and 8.86 for rat and human CGRP, respectively; thus the bovine retinal arteries cannot discriminate between CGRP from these two species. The CGRP-induced relaxation was reversible. Substance P was without effect on retinal arteries contracted with PGF2 alpha. Bradykinin relaxed 4 of 18 vessels tested in the concentration range of 11(-11)-10(-8) M whereas the vessels were contracted again at 3 x 10(-8) M. Bradykinin was without effect in the remaining 14 vessels. None of the peptides had a contractile effect on retinal arteries kept relaxed in normal buffer solution. Capsaicin 3 x 10(-5) M induced a relaxation comparable to that obtained by 10(-9) M of CGRP. The capsaicin-induced relaxation was reproducible and it was concentration dependently inhibited by ruthenium red which suggests that capsaicin releases CGRP in the arterial wall. The results indicate that CGRP has a powerful relaxing effect on the retinal vasculature indicating a role for CGRP in ocular blood flow regulation.