Arteriolar reactivity in vivo is influenced by an intramural diffusion barrier

1990 ◽  
Vol 259 (2) ◽  
pp. H574-H581 ◽  
Author(s):  
M. J. Lew ◽  
B. R. Duling
Keyword(s):  
Diffusion Barrier ◽  
Vascular Reactivity ◽  
Pressor Response ◽  
Systemic Blood Pressure ◽  
Water Soluble ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Water Soluble Drugs

The endothelium of the hamster cheek pouch arteriole in vitro is able to greatly reduce the potency of luminally applied water-soluble drugs by acting as a barrier to diffusion from the lumen to the smooth muscle [Lew, Rivers, and Duling. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H10-H16, 1989]. Lipid-soluble drugs appear unaffected by the diffusion barrier, presumably because their ability to cross cell membranes allows them to freely cross the endothelium. We compared the effects of two alpha 1-adrenoceptor agonists, phenylephrine (water soluble) and SKF 89748A (lipid soluble), on systemic blood pressure and the arterioles of the hamster cheek pouch in vivo. Both agonists were able to activate the arterioles when applied topically to the outside of the arterioles (extraluminal application). The agonists were also injected as a brief bolus into the aortic arch at doses chosen to elicit similar peak pressor responses. At all levels of pressor response, the arteriolar responses to phenylephrine were smaller than those to SKF 89748A. In the cremasteric vasculature SKF 89748A was similarly found to be more effective in activating the arterioles after intravascular administration than was phenylephrine. We conclude that an intramural diffusion barrier exists in the arteriolar wall in vivo and that it can influence vascular reactivity.

Vasodilation elicited by liposomal VIP is unimpeded by anti-VIP antibody in hamster cheek pouch

1998 ◽  
Vol 275 (1) ◽  
pp. R56-R62 ◽  
Author(s):  
Hiroyuki Ikezaki ◽  
Sudhir Paul ◽  
Hayat Alkan-Önyüksel ◽  
Manisha Patel ◽  
Xiao-Pei Gao ◽  
...  
Keyword(s):  
Calcium Ionophore ◽  
Myeloma Cell ◽  
Cheek Pouch ◽  
Myeloma Cell Line ◽  
Hamster Cheek Pouch ◽  
High Affinity ◽  
Sterically Stabilized Liposomes

The purpose of this study was to determine whether a monoclonal anti-vasoactive intestinal peptide (VIP) antibody, which binds VIP with high affinity and specificity and catalyzes cleavage of the peptide in vitro, attenuates VIP vasorelaxation in vivo and, if so, whether insertion of VIP on the surface of sterically stabilized liposomes (SSL), which protects the peptide from trypsin- and plasma-catalyzed cleavage in vitro, curtails this response. Using intravital microscopy, we found that suffusion of monoclonal anti-VIP antibody (clone c23.5, IgG2ak), but not of nonimmune antibody (myeloma cell line UPC10, IgG2ak) or empty SSL, significantly attenuates VIP-induced vasodilation in the in situ hamster cheek pouch ( P < 0.05). By contrast, anti-VIP antibody has no significant effects on vasodilation elicited by isoproterenol, nitroglycerin, and calcium ionophore A-23187, agonists that activate intracellular effector systems in blood vessels that mediate, in part, VIP vasoreactivity. Suffusion of VIP on SSL, but not of empty SSL, restores the vasorelaxant effects of VIP in the presence of anti-VIP antibody. Collectively, these data suggest that VIP catalysis by high affinity and specific VIP autoantibodies displaying protease-like activity constitutes a novel mechanism whereby VIP vasoreactivity is regulated in vivo.

Ratiometric measurement of endothelial depolarization in arterioles with a potential-sensitive dye

1996 ◽  
Vol 270 (6) ◽  
pp. H2216-H2227 ◽  
Author(s):  
J. M. Beach ◽  
E. D. McGahren ◽  
J. Xia ◽  
B. R. Duling
Keyword(s):  
Membrane Potential ◽  
Fluorescence Emission ◽  
Cheek Pouch ◽  
Voltage Sensitivity ◽  
Hamster Cheek Pouch ◽  
Endothelial Cell Layer ◽  
Ratiometric Measurement ◽  
Length Constant

A fluorescence ratio technique based on the voltage-sensitive dye 1-(3-sulfonatopropyl)-8-[beta-[2-di-n-butylamino)-6-naphythyl++ +]vinyl] pyridinium betaine (di-8-ANEPPS)has been developed for recording membrane potential changes during vascular responses of arterioles. Perfusion of hamster cheek pouch arterioles with the dye labeled the endothelial cell layer. voltage responses from the endothelium of intact arterioles were determined by analysis of voltage-induced shifts in fluorescence emission wavelengths from dye spectra imaged from the vessel wall. Membrane depolarization caused the dye spectrum to shift toward blue wavelengths, with maximal fluorescence changes near 560 and 620 nm. In isolated nonperfused arterioles, comparison of continuous dual-wavelength recordings with simultaneous microelectrode recordings showed that the ratio of fluorescence intensities (fluorescence at 620 nm to fluorescence at 560 nm) accurately followed changes in membrane potential (6–21 mV) during vasoconstriction. The dye response was linear with respect to potential changes from -56 to -6 mV, with a voltage sensitivity of 9.7% change in the ratio per 100 mV. Membrane potential responses from in vitro and in vivo arterioles after potassium stimulation consisted of rapid ( < 0.5 -s) depolarization followed by slow repolarization over several seconds. Potassium-induced depolarizations were conducted along arterioles, and the values of the electrical length constant for conducted depolarization determined by optical and microelectrode methods were in agreement. We conclude that ratio analysis of di-8-ANEPPS fluorescence emission can be used to accurately record membrane potential changes on the time scale of seconds during vasomotor activity from arterioles.

Arteriolar smooth muscle responses are modulated by an intramural diffusion barrier

1989 ◽  
Vol 257 (1) ◽  
pp. H10-H16 ◽  
Author(s):  
M. J. Lew ◽  
R. J. Rivers ◽  
B. R. Duling
Keyword(s):  
Smooth Muscle ◽  
Diffusion Barrier ◽  
Cell Layer ◽  
Water Soluble ◽  
Cheek Pouch ◽  
Physiological Salt Solution ◽  
Lipid Solubility ◽  
Hamster Cheek Pouch ◽  
Small Water ◽  
Sites Of Action

Arterioles (40–80 micron diameter) were isolated from the hamster cheek pouch, cannulated at both ends, and perfused with 3-(N-morpholino)propanesulfonic acid (MOPS)-buffered physiological salt solution (PSS). The vessels were observed with an inverted microscope and video system, and arteriolar diameter was measured. Arterioles were found to be 100 times more responsive to the alpha 1-adrenoceptor agonist phenylephrine when applied to the adventitial surface than when applied to the luminal surface. In contrast, SKF 89748-A, also an alpha 1-adrenoceptor selective agonist, but with a much greater lipid solubility than phenylephrine, was equipotent from either surface of the arteriole. We hypothesized that the difference between the two drugs was due to the ability of SKF 89748-A to permeate a diffusion barrier in the arteriolar wall because of its lipid-solubility. To test this hypothesis, a spectrum of antagonists with different sites of action and lipid solubilities was tested. The alpha-adrenoceptor antagonists phentolamine and benextramine and the muscarinic receptor antagonists atropine, scopolamine, and methscopolamine were all found to be more potent at blocking the action of appropriate agonists when applied to the same surface of the arteriole as the agonist than when applied to the opposite surface. Octanol-water partition coefficients were measured for each of the compounds, and these were found to be highly correlated with the ratio of luminal potency to adventitial potency for each of the drugs tested. These data support the hypothesis that the endothelial cell layer in these arterioles forms a barrier to the diffusion of small, water-soluble molecules from the lumen to the smooth muscle cell layer. Such a barrier may have a significant effect on arteriolar reactivity.

scholarly journals Studies on drug absorption from oral cavity. II Influence of the unstirred water layer on absorption from hamster cheek pouch in vitro and in vivo.

1987 ◽  
Vol 10 (4) ◽  
pp. 180-187 ◽  
Author(s):  
YUJI KUROSAKI ◽  
SHINICHI HISAICHI ◽  
CHIEKO HAMADA ◽  
TAIJI NAKAYAMA ◽  
TOSHIKIRO KIMURA
Keyword(s):  
Oral Cavity ◽  
Drug Absorption ◽  
Water Layer ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Unstirred Water Layer

scholarly journals Ternary Solid Dispersion Strategy for Solubility Enhancement of Poorly Soluble Drugs by Co-Milling Technique

2021 ◽  
Author(s):  
Marouene Bejaoui ◽  
Hanen Oueslati ◽  
Haykel Galai
Keyword(s):  
Solid Dispersion ◽  
Drug Carrier ◽  
Water Soluble ◽  
Pharmaceutical Ingredients ◽  
Drug Molecules ◽  
Water Soluble Drugs ◽  
Milling Method ◽  
Ternary Solid Dispersion

Amorphous ternary solid dispersion has become one of the strategies commonly used for improving the solubility and bioavailability of poorly water soluble drugs. Such multicomponent solid dispersion can be obtained by different techniques, this chapter provides an overview of ternary solid dispersion by co-milling method from the perspectives of physico-chemical characteristics in vitro and in vivo performance. A considerable improvement of solubility was obtained for many active pharmaceutical ingredients (e.g., Ibuprofen, Probucol, Gliclazid, Fenofibrate, Ibrutinib and Naproxen) and this was correlated to the synergy of multiple factors (hydrophilicity enhancement, particle size reduction, drug-carrier interactions, anti-plasticizing effect and complexation efficiency). This enhanced pharmacokinetic properties and bioavailability of these drug molecules (1.49 to 15-folds increase in plasma drug concentration). A particular focus was accorded to compare the ternary and binary system including Ibuprofen and highlighting the contribution of thermal and spectral characterization techniques. The addition of polyvinylpyrrolidone (PVP K30), a low molecular weight molecule, into the binary solid dispersion (Ibuprofen/β-cyclodextrin), leads to a 1.5–2 folds increase in the drug intrinsic dissolution rate only after 10 min. This resulted from physical stabilization of amorphous Ibuprofen by reducing its molecular mobility and inhibiting its recristallization even under stress conditions (75% RH and T = 40°C for six months).

Use of in vitro lipid digestion data to explain the in vivo performance of triglyceride-based oral lipid formulations of poorly water-soluble drugs: Studies with halofantrine

2004 ◽  
Vol 93 (5) ◽  
pp. 1110-1121 ◽  
Author(s):  
Christopher J.H. Porter ◽  
Ann Marie Kaukonen ◽  
Agnes Taillardat-Bertschinger ◽  
Ben J. Boyd ◽  
Jacquelyn M. O'Connor ◽  
...  
Keyword(s):  
Water Soluble ◽  
Lipid Digestion ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Lipid Formulations

scholarly journals Development of a New Ex Vivo Lipolysis-Absorption Model for Nanoemulsions

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 164 ◽  
Author(s):  
Lu Xiao ◽  
Ying Liu ◽  
Tao Yi
Keyword(s):  
Ex Vivo ◽  
Water Soluble ◽  
Absorption Model ◽  
Poorly Water Soluble Drugs ◽  
Everted Gut Sac ◽  
In Vivo Absorption ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble

The use of lipid-based formulations (LBFs) in improving the absorption of poorly water-soluble drugs has now well established. Because the in vivo evaluation of LBFs is labor-intensive, in vitro or ex vivo approaches could provide advantages. In this study, a new ex vivo lipolysis-absorption model (evLAM) composed of an intestinal digestion system and an intestinal tissue system was developed to evaluate and predict the in vivo absorption performances of LBFs. Model factors, including the pH of the system and concentrations of d-glucose and pancreatic lipase, were investigated and optimized by a Box-Behnken design. To evaluate this new model, a lipid formulation of indomethacin, which was chosen based on preliminary studies of pseudo-ternary phase diagrams, emulsion droplets, and solubility, was further investigated by an in vivo pharmacokinetic study of rats, the everted gut sac model, and the evLAM, respectively. The absorption percentages obtained from the evLAM were much more similar to the data of rats in vivo than those from the everted gut sac model, showing a preferable in vitro-in vivo correlation (r = 0.9772). Compared with the conventional in vitro and in vivo methods, the evLAM, which allowed precise insights into the in vivo absorption characteristics without much time or a complicated process, could be a better tool for assessing LBFs of poorly water-soluble drugs.

Sign in / Sign up

Export Citation Format

Share Document