Reduced responses of retinal vessels of the newborn pig to prostaglandins but not to thromboxane

1994 ◽  
Vol 72 (2) ◽  
pp. 168-173 ◽  
Author(s):  
Daniel Abran ◽  
Daya R. Varma ◽  
Ding-You Li ◽  
Sylvain Chemtob
Keyword(s):  
Blood Flow ◽  
Receptor Agonist ◽  
Perfusion Pressure ◽  
Retinal Blood Flow ◽  
Receptor Subtype ◽  
Retinal Vasculature ◽  
Receptor Subtypes ◽  
Retinal Vessels ◽  
Limit Blood Flow ◽  
Arteries And Veins

The upper blood pressure limit of retinal blood flow autoregulation is lower in the newborn than in the adult; this suggests an insufficient vasoconstrictor response in the newborn when perfusion pressure is increased. Because prostaglandins (PGs) have an important role in autoregulation of retinal blood flow, we compared the effects of PGE2, PGF2α, carbacyclin (PGI2 analogue), and U46619 (thromboxane analogue), as well as that of agonists for the three different PGE2 receptor subtypes, 17-phenyl trinor PGE2 (EP1), butaprost (EP2), and M&B 28,767 (EP3), on the retinal vasculature of newborn and adult pigs, using isolated eyecup preparations. PGF2α and PGE2 caused a markedly greater constriction of retinal arteries and veins of the adult than of the newborn animals. Further analysis of the response to PGE2, using receptor subtype agonists, revealed that the EP1 receptor agonist, 17-phenyl trinor PGE2, and the EP3 receptor agonist, M&B 28,767, caused a significant constriction of adult arteries and veins but produced minimal effects on newborn vessels; the EP2 receptor agonist, butaprost, caused a small and comparable dilation of newborn and adult arteries and veins. The PGI2 analogue, carbacyclin, caused a greater dilation of the adult than of the newborn arteries, but produced comparable dilation of veins from both newborn and adult animals. In contrast to the effects of PGF2α and PGE2, the thromboxane analogue, U46619, as well as the α1-adrenoceptor agonist, phenylephrine, significantly constricted newborn arteries and veins, and this effect was comparable with that observed on retinal vessels of the adult. Our findings indicate that the retinal vasculature of the newborn responds minimally to prostaglandins, primarily PGF2α and PGE2, compared with the adult, but constricts effectively to thromboxane. Since prostaglandins play an important role in the autoregulation of retinal blood flow, our observations provide an explanation for the inability of the newborn to limit blood flow when perfusion pressure is raised.Key words: retinal vascular responses, prostaglandins, thromboxane, PGE2 receptor subtypes.

scholarly journals Vasoactive intestinal peptide (VIP) stimulates cortisol secretion from the H295 human adrenocortical tumour cell line via VPAC1 receptors

2004 ◽  
Vol 32 (3) ◽  
pp. 869-877 ◽  
Author(s):  
MR Nicol ◽  
VJ Cobb ◽  
BC Williams ◽  
SD Morley ◽  
SW Walker ◽  
...  
Keyword(s):  
Cell Line ◽  
Vasoactive Intestinal Peptide ◽  
Receptor Agonist ◽  
Threshold Dose ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Cortisol Secretion ◽  
Maximal Dose ◽  
Vpac1 Receptor ◽  
Dose Dependent

Vasoactive intestinal peptide (VIP) shows a wide tissue distribution and exerts numerous physiological actions. VIP was shown in a dose-dependent manner to increase cortisol secretion in the NCI-H295R human adrenocortical carcinoma (H295) cell line (threshold dose 3.3x10(-10) M, maximal dose 10(-7) M), coupled with a parallel increase in cAMP accumulation. Receptor-specific agonists were employed to determine which of the two known VIP receptor subtypes was involved in cortisol secretion. Treatment with the VPAC1 receptor agonist, [K(15), R(16), L(27)]VIP(1-7)/GRF(8-27), produced a dose-dependent increase in H295 cell cortisol secretion (threshold dose 10(-11) M, maximal dose 10(-7) M) similar to that seen with VIP. Meanwhile, the high-affinity VPAC2 receptor agonist, RO-25-1553, failed to stimulate significantly cortisol or cAMP production from H295 cells. Inhibition of VIP-mediated H295 cell cortisol secretion by PG97-269, a competitive VPAC1-specific antagonist, produced parallel shifts of the dose-response curve and a Schild regression slope of 0.99, indicating competitive inhibition at a single receptor subtype. VIP is known also to interact with the PAC1 receptor, albeit with lower affinity (EC(50) of approximately 200 nM) than the homologous ligand, PACAP (EC(50) of approximately 0.5 nM). PACAP stimulated cortisol secretion from H295 cells (EC(50) of 0.3 nM), suggesting the presence of functional PAC1 receptors. However, stimulation of cortisol secretion by nanomolar concentrations of VIP (EC(50) of 5 nM), coupled with real-time PCR estimation that VPAC1 receptor transcripts appear 1000-fold more abundant than PAC1 transcripts in H295 cells, makes it unlikely that VIP signals via PAC1 receptors. Together, these data suggest that VIP directly stimulates cortisol secretion from H295 cells via activation of the VPAC1 receptor subtype.

scholarly journals Functional Hyperemia and Mechanisms of Neurovascular Coupling in the Retinal Vasculature

2013 ◽  
Vol 33 (11) ◽  
pp. 1685-1695 ◽  
Author(s):  
Eric A Newman
Keyword(s):  
Blood Flow ◽  
Glial Cells ◽  
Neurovascular Coupling ◽  
Retinal Blood Flow ◽  
Retinal Vasculature ◽  
Functional Hyperemia ◽  
Cellular Mechanisms ◽  
Neuronal Stimulation ◽  
Health And Disease ◽  
Coupling Mechanisms

The retinal vasculature supplies cells of the inner and middle layers of the retina with oxygen and nutrients. Photic stimulation dilates retinal arterioles producing blood flow increases, a response termed functional hyperemia. Despite recent advances, the neurovascular coupling mechanisms mediating the functional hyperemia response in the retina remain unclear. In this review, the retinal functional hyperemia response is described, and the cellular mechanisms that may mediate the response are assessed. These neurovascular coupling mechanisms include neuronal stimulation of glial cells, leading to the release of vasoactive arachidonic acid metabolites onto blood vessels, release of potassium from glial cells onto vessels, and production and release of nitric oxide (NO), lactate, and adenosine from neurons and glia. The modulation of neurovascular coupling by oxygen and NO are described, and changes in functional hyperemia that occur with aging and in diabetic retinopathy, glaucoma, and other pathologies, are reviewed. Finally, outstanding questions concerning retinal blood flow in health and disease are discussed.

scholarly journals Differences of Retinal Blood Flow Between Arteries and Veins Determined by Laser Speckle Flowgraphy in Healthy Subjects

Medicine ◽  
2015 ◽  
Vol 94 (33) ◽  
pp. e1256 ◽  
Author(s):  
Takeshi Iwase ◽  
Eimei Ra ◽  
Kentaro Yamamoto ◽  
Hiroki Kaneko ◽  
Yasuki Ito ◽  
...  
Keyword(s):  
Blood Flow ◽  
Healthy Subjects ◽  
Laser Speckle ◽  
Retinal Blood Flow ◽  
Laser Speckle Flowgraphy ◽  
Arteries And Veins

Modulation of Spontaneous Firing in Rat Subthalamic Neurons by 5-HT Receptor Subtypes

2005 ◽  
Vol 93 (3) ◽  
pp. 1145-1157 ◽  
Author(s):  
Zixiu Xiang ◽  
Lie Wang ◽  
Stephen T. Kitai
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Driving Forces ◽  
Brain Slices ◽  
Potassium Conductance ◽  
Firing Frequency ◽  
Membrane Properties ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Membrane Excitability

The subthalamic nucleus (STN) is considered to be one of the driving forces in the basal ganglia circuit. The STN is innervated by serotonergic afferents from the raphe nucleus and expresses a variety of 5-HT receptor subtypes. We investigated the effects of 5-HT and 5-HT receptor subtype agonists and antagonists on the firing properties of STN neurons in rat brain slices. We used cell-attached, perforated-patch, and whole cell recording techniques to detect changes in firing frequency and pattern and electrical membrane properties. Due to the depolarization of membrane potential caused by reduced potassium conductance, 5-HT (10 μM) increased the firing frequency of STN neurons without changing their firing pattern. Cadmium failed to occlude the effect of 5-HT on firing frequency. 5-HT had no effect on afterhyperpolarization current. These results indicated that the 5-HT action was not mediated by high-voltage–activated calcium channel currents and calcium-dependent potassium currents. 5-HT had no effect on hyperpolarization-activated cation current ( IH) amplitude and voltage-dependence of IH activation, suggesting that IH was not involved in 5-HT–induced excitation. The increased firing by 5-HT was mimicked by 5-HT2/4 receptor agonist α-methyl-5-HT and was partially mimicked by 5-HT2 receptor agonist DOI or 5-HT4 receptor agonist cisapride. The 5-HT action was partially reversed by 5-HT4 receptor antagonist SB 23597-190, 5-HT2 receptor antagonist ketanserin, and 5-HT2C receptor antagonist RS 102221. Our data indicate that 5-HT has significant ability to modulate membrane excitability in STN neurons; modulation is accomplished by decreasing potassium conductance by activating 5-HT4 and 5-HT2C receptors.

Major role for neuronal NO synthase in curtailing choroidal blood flow autoregulation in newborn pig

2001 ◽  
Vol 91 (4) ◽  
pp. 1655-1662 ◽  
Author(s):  
P. Hardy ◽  
D. Lamireau ◽  
X. Hou ◽  
I. Dumont ◽  
D. Abran ◽  
...  
Keyword(s):  
Blood Flow ◽  
Perfusion Pressure ◽  
Narrow Range ◽  
No Synthase ◽  
Retinal Blood Flow ◽  
Choroidal Blood Flow ◽  
Neuronal No Synthase ◽  
Nos Inhibitors ◽  
Newborn Pigs ◽  
Hemodynamic Function

We examined whether nitric oxide (NO) generated from neuronal NO synthase (nNOS) contributes to the reduced ability of the newborn to autoregulate retinal blood flow (RBF) and choroidal blood flow (ChBF) during acute rises in perfusion pressure. In newborn pigs (1–2 days old), RBF (measured by microsphere) is autoregulated over a narrow range of perfusion pressure, whereas ChBF is not autoregulated. N G-nitro-l-arginine methyl ester (l-NAME) or specific nNOS inhibitors 7-nitroindazole, 3-bromo-7-nitroindazole, and 1-(2-trifluoromethyl-phenyl)imidazole as well as ganglionic blocker hexamethonium, unveiled a ChBF autoregulation as observed in juvenile (4- to 6-wk old) animals, whereas autoregulation of RBF in the newborn was only enhanced byl-NAME. All NOS inhibitors and hexamethonium prevented the hypertension-induced increase in NO mediator cGMP in the choroid. nNOS mRNA expression and activity were three- to fourfold higher in the choroid of newborn pigs than in tissues of juvenile pigs. It is concluded that increased production of NO from nNOS curtails ChBF autoregulation in the newborn and suggests a role for the autonomic nervous system in this important hemodynamic function, whereas, for RBF autoregulation, endothelial NOS seems to exert a more important contribution in limiting autoregulation.

Differential Distribution of 5Ht1D-and 5HT1B-Immunoreactivity within the Human Trigemino-Cerebrovascular System: Implications for the Discovery of New Antimigraine Drugs

Cephalalgia ◽  
1997 ◽  
Vol 17 (8) ◽  
pp. 833-842 ◽  
Author(s):  
J Longmore ◽  
D Shaw ◽  
D Smith ◽  
R Hopkins ◽  
G McAlliste ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Receptor Agonist ◽  
Sensory System ◽  
Receptor Protein ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Therapeutic Action ◽  
Differential Distribution ◽  
Antimigraine Drugs ◽  
Cerebrovascular System

Sumatriptan, a 5HT1B/1D-receptor agonist, is clinically effective as an antimigraine agent. Its therapeutic action may result partly from vasoconstriction of excessively dilated cranial blood vessels (a 5HT1B-receptor mediated response). The antimigraine activity of sumatriptan may also result from inhibition of the release of vasoactive neuropeptides from trigeminal sensory fibres within the meninges. The identity of the 5HT1B/1D-receptor subtype mediating this effect is unknown. Using 5HT1D- and 5HT1B-receptor-specific antibodies we have demonstrated a differential distribution of these receptor subtypes within the human trigemino-cerebrovascular system. Only 5HT1B-receptor protein was detected on dural arteries. In contrast, only 5HT1D-receptor protein was detected on trigeminal sensory neurones including peripheral and central projections to dural blood vessels and to the medulla. Within the medulla 5HT1D-receptor protein was confined to discrete areas associated with the trigeminal sensory system. These findings have important implications for the design of new antimigraine drugs.

scholarly journals Hypothesis: Vasoconstriction Contributes to Amaurosis Fugax

1989 ◽  
Vol 9 (1) ◽  
pp. 111-116 ◽  
Author(s):  
J. Koudy Williams ◽  
Gary L. Baumbach ◽  
Mark L. Armstrong ◽  
Donald D. Heistad
Keyword(s):  
Blood Flow ◽  
Critical Role ◽  
Experimental Atherosclerosis ◽  
Retinal Blood Flow ◽  
Retinal Vessels ◽  
Amaurosis Fugax ◽  
Retinal Circulation ◽  
Cynomolgus Monkeys ◽  
Vasoactive Substances ◽  
Retinal Response

Platelets play a critical role in the pathophysiology of amaurosis fugax. Emboli to retinal vessels apparently produce amaurosis but, in addition, we propose that augmented vasoconstrictor responses and vasospasm may contribute to amaurosis. In this study we tested the hypothesis that constrictor responses of retinal vessels to serotonin, which is released when platelets aggregate, are potentiated in experimental atherosclerosis. Blood flow to the retina was measured in normal and atherosclerotic cynomolgus monkeys. In normal monkeys, infusion of serotonin did not alter flow to the retina. In atherosclerotic monkeys, infusion of serotonin reduced retinal blood flow (in milliliters per minute per 100 g) from 66 ± 7 (mean ± SE) to 5 ±2. Infusion of serotonin in atherosclerotic monkeys abolished the retinal response to light. Thus, atherosclerosis greatly potentiates constrictor responses to serotonin in the retinal circulation and produces a profound but reversible impairment of retinal function. We propose that altered responses to vasoactive substances that are released by platelets may contribute to the pathogenesis of amaurosis fugax.

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