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

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.

scholarly journals Studies on drug absorption from oral cavity: physico-chemical factors affecting absorption from hamster cheek pouch.

1986 ◽  
Vol 9 (3) ◽  
pp. 287-296 ◽  
Author(s):  
YUJI KUROSAKI ◽  
NORIKO(YAMASHITA AYA ◽  
YUMIKO OKADA ◽  
TAIJI NAKAYAMA ◽  
TOSHIKIRO KIMURA
Keyword(s):  
Oral Cavity ◽  
Drug Absorption ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Factors Affecting ◽  
Physico Chemical ◽  
Chemical Factors

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.

scholarly journals The Effect of Prostaglandins G2, D2, E2, E1 and Arachidonic acid on Thrombus Formation in Vivo

1977 ◽  
Author(s):  
J. Westwick ◽  
G.P. Lewis
Keyword(s):  
Arachidonic Acid ◽  
Thrombus Formation ◽  
Cheek Pouch ◽  
Mural Thrombus ◽  
Hamster Cheek Pouch ◽  
Potent Vasodilator ◽  
High Doses

Arachidonic acid (AA) and prostaglandin (PG) G2 have been shown to he precursors of both pro-aggregatory and anti-aggregatory agents in vitro. If PGG2 is produced in thrombotic and inflammatory situations, it is important to know its effects on thrombus formation in vivo. Mural thrombus formation was induced in the arterioles (40-70 μm) of the hamster cheek pouch by combining micro-electrical damage with perivascular application of ADP (10-6M).PG or vehicle was applied perivascularly, followed 30 sec and 1 min later by electrical micro-damage and application of ADP (lOM). The vessel was observed and thrombus formation was quantitated by timing the adherence of thrombi for the following 10 nriruEach animal served as its own control and results were expressed as % difference (mean - s.e.) from control. PGGs, AA and PGE]_ produced a dose-related (12.5 - 1250 ng) inhibition (lO ± 8% - 90 ± 15%) of thrombus formation.Both PGG2 (Lewis, Vestwick & Williams, Br.J.Pharmac., 1977, in press) and AA induce a short-lasting vasoconstriction followed by vasodilatation. However, another potent vasodilator, PGE1, in a low Jose (125 ng) potentiated (49 - 20%) while high doses (1250 ng) produced a weak inhibition (15 ± 10%) of thrombus formation. PGD2 had little activity up to a concentration of I25O ng.These results demonstrate that AA and PGG2 can be converted to anti-thrombotic agents in vivo when applied perivascularly. Since PGD5 and PGE2 were not anti-thrombotic, it is possible that the observed effect was due to generation of prostacyclin.

Arteriolar smooth muscle Ca2+ dynamics during blood flow control in hamster cheek pouch

2006 ◽  
Vol 101 (1) ◽  
pp. 307-315 ◽  
Author(s):  
Johan Fredrik Brekke ◽  
William F. Jackson ◽  
Steven S. Segal
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Local Control ◽  
Cheek Pouch ◽  
Tissue Blood Flow ◽  
Hamster Cheek Pouch ◽  
Dye Loading ◽  
Blood Flow Control

Intracellular calcium concentration ([Ca2+]i) governs the contractile status of arteriolar smooth muscle cells (SMC). Although studied in vitro, little is known of SMC [Ca2+]i dynamics during the local control of blood flow. We tested the hypothesis that the rise and fall of SMC [Ca2+]i underlies arteriolar constriction and dilation in vivo. Aparenchymal segments of second-order arterioles (diameter 35 ± 2 μm) were prepared in the superfused cheek pouch of anesthetized hamsters ( n = 18) and perifused with the ratiometric dye fura PE-3 (AM) to load SMC (1 μM, 20 min). Resting SMC [Ca2+]i was 406 ± 37 nM. Elevating superfusate O2 from 0 to 21% produced constriction (11 ± 2 μm) that was unaffected by dye loading; [Ca2+]i increased by 108 ± 53 nM ( n = 6, P < 0.05). Cycling of [Ca2+]i during vasomotion (amplitude, 150 ± 53 nM; n = 4) preceded corresponding diameter changes (7 ± 1 μm) by ∼2 s. Microiontophoresis (1 μm pipette tip; 1 μA, 1 s) of phenylephrine (PE) transiently increased [Ca2+]i by 479 ± 64 nM ( n = 8, P < 0.05) with constriction (26 ± 3 μm). Flushing blood from the lumen with saline increased fluorescence at 510 nm by ∼45% during excitation at both 340 and 380 nm with no difference in resting [Ca2+]i, diameter or respective responses to PE ( n = 7). Acetylcholine microiontophoresis (1 μA, 1 s) transiently reduced resting SMC [Ca2+]i by 131 ± 21 nM ( n = 6, P < 0.05) with vasodilation (17 ± 1 μm). Superfusion of sodium nitroprusside (10 μM) transiently reduced SMC [Ca2+]i by 124 ± 18 nM ( n = 6, P < 0.05), whereas dilation (23 ± 5 μm) was sustained. Resolution of arteriolar SMC [Ca2+]i in vivo discriminates key signaling events that govern the local control of tissue blood flow.

Components of methacholine-initiated conducted vasodilation are unaffected by arteriolar pressure

1997 ◽  
Vol 272 (6) ◽  
pp. H2895-H2901 ◽  
Author(s):  
R. J. Rivers
Keyword(s):  
Average Length ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Electromechanical Transduction ◽  
Isolated Segment ◽  
A Site ◽  
Conducted Response

Conducted vasodilation occurs remotely from a site of microapplication of a drug. Intravascular pressure is required for a conducted response in vivo, yet in vitro studies in unpressurized arterioles show pressure is not essential. To determine how pressure affects conducted vasodilation, intra-arteriolar pressure was controlled within an in situ isolated segment (average length 950 +/- 96 microns, average baseline diameter 28 +/- 2.1 microns) of arterioles in the hamster cheek pouch. Methacholine (10(-4) M, 5 s) was microapplied either onto the isolated segment or remotely, with local and conducted vasodilation measured at both locations. Increasing pressure in the lumen of the segment (0-80 cmH2O) increased the segment local dilation to methacholine, and the segment-conducted dilation plateaued (at 4.1 +/- 0.8 micron) when segment pressure reached 20 cmH2O. Any local (16 +/- 1.5 microns) and conducted (4.4 +/- 1.3 microns) dilations viewed outside the segment were unaffected by segment pressure and persisted in its absence. Thus segment pressure affected only electromechanical transduction of the conducted response. Thus vasomotor signals move throughout the vasculature regardless of tone, but tone is essential to transduce the response.

Jejunal uptake of sugars, cholesterol, fatty acids, and fatty alcohols in vivo in diabetic rats

1985 ◽  
Vol 63 (11) ◽  
pp. 1356-1361
Author(s):  
C. Hotke ◽  
Y. McIntyre ◽  
A. B. R. Thomson
Keyword(s):  
Fatty Acids ◽  
Lauric Acid ◽  
Water Layer ◽  
Diabetic Rats ◽  
The Body ◽  
Unstirred Layer ◽  
Unstirred Water Layer ◽  
Uptake Of Nutrients

Previous in vitro studies have demonstrated enhanced active and passive intestinal uptake of nutrients in streptozotocin-diabetic rats, but the effect of diabetes on the in vivo absorption of glucose and amino acids remains controversial, and the effect of diabetes on the in vivo uptake of lipids has not been reported. Accordingly, an in vivo perfusion technique was used in rats to examine the uptake of nutrients from the intestinal lumen, their transfer to the body, their mucosal and submucosal content, and the percentage of uptake transferred. Diabetes was associated with reduced uptake of fatty alcohols, indicating that the effective resistance of the unstirred water layer in vivo is higher in diabetic than in nondiabetic control rats. The mucosal and submucosal content of dodecanol was lower in diabetic than in control rats, but the percentage of the dodecanol uptake transferred to the body was higher. Although the uptake of varying concentrations of D-galactose was similar in diabetic and in control animals, kinetic analysis corrected for unstirred layer effects demonstrated lower mean values of the passive permeability coefficients (Pd) for galactose in diabetic than in control animals, with lower values of the Michaelis constant (Km) and higher values of the maximal transport rate [Formula: see text]. The uptake of lauric acid was reduced in diabetic rats, whereas the uptake of deconoic acid and of cholesterol was unchanged. With correction for unstirred layer effects, it was apparent that the jejunum of diabetic rats was in fact more permeable to decanoic and lauric acid as well as to cholesterol. The results suggest that (i) in diabetic rats the effective resistance of the unstirred water layer between the jejunal lumen and the brush border membrane is lower; (ii) the differences in unstirred layer resistance between the diabetic and control animals obscure the changes in the kinetic constants (Pd, Km, [Formula: see text]) describing the uptake of galactose, medium chain length fatty acids and cholesterol; and (iii) the kinetic changes in nutrient uptake observed in vitro may be confirmed in vivo once the effect of intestinal unstirred layers has been taken into account.

scholarly journals Intestinal absorption of linoleic acid in experimental renal failure

1991 ◽  
Vol 66 (3) ◽  
pp. 467-477
Author(s):  
M. V. Pahl ◽  
A. Barbari ◽  
N. D. Vaziri ◽  
D. Hollander ◽  
M. Yazdani ◽  
...  
Keyword(s):  
Renal Failure ◽  
Linoleic Acid ◽  
Water Layer ◽  
Short Term ◽  
Unstirred Water Layer ◽  
Wide Range ◽  
Significant Difference

Linoleic acid (LA) transport in rats with experimental short-term and long-term renal failure (RF) was compared with that of sham-operated normal animals on liberal food intake and pair-fed animals. The perfusions in vivo and incubations in vitro were conducted using a micellar solution containing a wide range of LA concentrations. Both absorption in vivo and uptake in vitro of LA were significantly reduced in animals with short-term RF. Lipid extraction and separation by thin-layer chromatography revealed a marked LA trapping as trilinolein (TL) in the perfused intestinal tissue in the short-term RF group. The esterification process, as defined by the rate of LA incorporation into TL, was moderately reduced in short-term RF animals. The thickness of the unstirred water layer showed no significant difference among the groups studied. In contrast, animals with long-term RF exhibited normal absorption of LA in vivo at all concentrations tested. In conclusion, LA absorption is reduced in short-term RF and restored in long-term RF. Several steps including LA transport into and TL transport out of the enterocyte and the esterification process were impaired in short-term RF. These changes are not due to alteration in the unstirred water layer, anorexia, weight loss or a rapid effect of uraemic chemical environment or circulatory factors.

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