Vasoactive intestinal polypeptide reduces hydrochloric acid-induced duodenal mucosal permeability

1993 ◽  
Vol 264 (2) ◽  
pp. G272-G279 ◽  
Author(s):  
O. Nylander ◽  
E. Wilander ◽  
G. M. Larson ◽  
L. Holm

The duodenum in anesthetized rats was perfused with HCl, and mucosal integrity was assessed by measuring the clearance of 51Cr-labeled EDTA from blood to lumen and/or by morphological examination (lesion score). Duodenal blood flow was determined by laser Doppler flowmetry and luminal alkalinization as well as H+ disappearance by backtitration. Intravenous infusion of vasoactive intestinal polypeptide (VIP; 13.5 micrograms.kg-1.h-1) increased luminal alkalinization threefold and decreased clearance of 51Cr-EDTA by 50%. VIP also decreased arterial blood pressure and induced a small and irregular decrease in duodenal blood flow. Perfusion with 10 mM HCl increased clearance of 51Cr-EDTA 2.1-fold, but the lesion score was not different from that in saline-perfused animals. Perfusion with 20 mM HCl increased clearance of 51Cr-EDTA four-fold and induced a greater lesion score than did 10 mM. Perfusion with either 10 or 20 mM HCl did not affect the duodenal blood flow. VIP reduced the rise in clearance of 51Cr-EDTA in response to 10 mM but not that to 20 mM HCl. Intravenous injection of prazosin (50 micrograms/kg) decreased luminal alkalinization, clearance of 51Cr-EDTA, blood pressure, and duodenal blood flow. In prazosin-pretreated rats, perfusion with 10 mM HCl increased clearance of 51Cr-EDTA 2.6-fold, and the lesion score was greater in this group than in animals infused with VIP. A positive linear correlation was obtained between HCO3- secretion and the mean rate of H+ disappearance.(ABSTRACT TRUNCATED AT 250 WORDS)

1993 ◽  
Vol 265 (6) ◽  
pp. G1029-G1038 ◽  
Author(s):  
O. Nylander ◽  
A. Hallgren ◽  
L. Holm

The relationship between duodenal mucosal alkaline secretion, permeability, and blood flow was examined in anesthetized rats. Duodenum was perfused with saline, and rate of luminal alkalinization (LA), mucosal permeability (clearance of 51Cr-EDTA from blood to lumen), effluent volume, mean arterial blood pressure (MABP), and blood flow (laser-Doppler flowmetry) were determined. Infusion of vasoactive intestinal polypeptide (VIP, 13.5 micrograms.kg-1 x h-1 i.v.) increased LA and fluid secretion but decreased MABP and mucosal permeability. The concentration of base in the secreted fluid was 45 mM. Systemic infusion of VIP (2.5 micrograms.kg-1 x h-1) increased LA and fluid secretion; the HCO3- concentration in secreted fluid was 86 mM. The lower VIP dose affected neither blood flow nor mucosal permeability. Both intravenous (10 mg/kg + 3 mg.kg-1 x h-1) and intraluminal (3 x 10(-3) M) N omega-nitro-L-arginine (L-NNA) increased LA and effluent volume; the HCO3- concentration in the secreted fluid was 38 and 44 mM, respectively. Intravenous, but not intraluminal, L-NNA increased mucosal permeability and decreased blood flow. Reduction of arterial blood pressure by blood withdrawal or by injection of prazosin (50 micrograms/kg i.v.) or hexamethonium (20 mg/kg i.v.) decreased LA and mucosal permeability. Prazosin decreased blood flow, whereas hexamethonium slightly increased blood flow. We conclude that NO may be an inhibitory regulator of LA and that both L-NNA and VIP increase LA via stimulation of active HCO3- transport. VIP probably increases HCO3- and fluid secretion by two separate ion transport mechanisms. No causal relationship exists between LA and blood flow, between LA and mucosal permeability, or between mucosal permeability and blood flow. A positive linear correlation exists between MABP and mucosal permeability, suggesting that marked changes of MABP may influence permeation of small water-soluble solutes across duodenal mucosa.


2005 ◽  
Vol 289 (4) ◽  
pp. H1662-H1668 ◽  
Author(s):  
C. A. Wauschkuhn ◽  
K. Witte ◽  
S. Gorbey ◽  
B. Lemmer ◽  
L. Schilling

Cardiovascular parameters such as arterial blood pressure (ABP) and heart rate display pronounced circadian variation. The present study was performed to detect whether there is a circadian periodicity in the regulation of cerebral perfusion. Normotensive Sprague-Dawley rats (SDR, ∼15 wk old) and hypertensive (mREN2)27 transgenic rats (TGR, ∼12 wk old) were instrumented in the abdominal aorta with a blood pressure sensor coupled to a telemetry system for continuous recording of ABP, heart rate, and locomotor activity. After 5–12 days, a laser-Doppler flow (LDF) probe was attached to the skull by means of a guiding device to measure changes in brain cortical blood flow (CBF). After the animals recovered from anesthesia, measurements were taken for 3–4 days. The time series were analyzed with respect to the midline estimating statistic of rhythm (i.e., mean value of a periodic event after fit to a cosine function), amplitude, and acrophase (i.e., phase angle that corresponds to the peak of a given period) of the 24-h period. The LDF signal displayed a significant circadian rhythm, with the peak occurring at around midnight in SDR and TGR, despite inverse periodicity of ABP in TGR. This finding suggests independence of LDF periodicity from ABP regulation. Furthermore, the acrophase of the LDF was consistently found before the acrophase of the activity. From the present data, it is concluded that there is a circadian periodicity in the regulation of cerebral perfusion that is independent of circadian changes in ABP and probably is also independent of locomotor activity. The presence of a circadian periodicity in CBF may have implications for the occurrence of diurnal alterations in cerebrovascular events in humans.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Sourav Kundu ◽  
Sathnur Pushpakumar ◽  
Naira Metriveli ◽  
Suresh C Tyagi ◽  
Utpal Sen

High salt diet has long been associated with chronic hypertension. The development of renal injury in Dahl salt-sensitive (SS) hypertensive rats is characterized by structural and functional changes involving vascular remodeling. Increased activity of matrix metalloproteinases (MMPs) leading to alteration in the extracellular matrix (ECM) is the main mechanism contributing to increased peripheral vascular resistance. In this study, we hypothesized that inhibition of MMPs will modulate ECM remodeling by decreasing MMP activity and thus reduce mean arterial blood pressure. METHODS: We used Dahl-salt sensitive (Dahl-SS) and Lewis rats fed on high salt diet. The groups were 1) Dahl-SS, 2) Dahl-SS+GM6001 (non-specific MMP inhibitor), 3) Lewis, and 4) Lewis+GM6001. GM6001 was given at 0.5mg/mL by intra-peritoneal injection on alternate days for 3 weeks. Blood pressure, laser doppler flowmetry for renal cortical blood flow and barium angiography for renal vascular density were measured. Results: Mean arterial blood pressure was 172.10 ± 0.57 mm Hg in hypertensive Dahl-SS rats compared to 136.12 ± 1.22 mm Hg in Dahl-SS+GM6001 rats. The mean arterial pressures in lewis and lewis+GM6001 groups were 97.08 ± 0.56 and 87.63 ± 2.93 mm Hg respectively. Laser doppler flowmetry showed reduced renal cortical blood flow (1333.33 flux units) in Dahl-SS rats compared to Dahl-SS rats treated with GM6001 (1605 flux units). Lewis rats showed similar renal cortical flow with (1488.33 flux units) or without GM6001 (1425 flux units). Barium angiography demonstrated increased renal vascular density with patent branches in the renal cortex of animals treated with MMP inhibitor, GM6001. Conclusion: Our results suggest that in hypertensive Dahl-SS rats, inhibition of MMP attenuates high blood pressure, maintains patency of renal cortical vessels thus improving cortical blood flow.


2007 ◽  
Vol 293 (6) ◽  
pp. G1281-G1287 ◽  
Author(s):  
Joel Petersson ◽  
Olof Schreiber ◽  
Andreas Steege ◽  
Andreas Patzak ◽  
Anna Hellsten ◽  
...  

The role of NO in inflammatory bowel disease is controversial. Studies indicate that endothelial nitric oxide synthase (eNOS) might be involved in protecting the mucosa against colonic inflammation. The aim of this study was to investigate the involvement of nitric oxide (NO) in regulating colonic mucosal blood flow in two different colitis models in rats. In anesthetized control and colitic rats, the distal colon was exteriorized and the mucosa visualized. Blood flow (laser-Doppler flowmetry) and arterial blood pressure were continuously monitored throughout the experiments, and vascular resistance was calculated. Trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS) was used to induce colitis. All groups were given the NOS inhibitor Nω-nitro-l-arginine (l-NNA) or the inducible NOS (iNOS) inhibitor l- N6-(1-iminoethyl)-lysine (l-NIL). iNOS, eNOS, and neuronal NOS (nNOS) mRNA in colonic samples were investigated with real-time RT-PCR. Before NOS inhibition, colonic mucosal blood flow, expressed as perfusion units, was higher in both colitis models compared with the controls. The blood flow was reduced in the TNBS- and DSS-treated rats during l-NNA administration but was not altered in the control group. Vascular resistance increased more in the TNBS- and DSS-treated rats than in the control rats, indicating a higher level of vasodilating NO in the colitis models. l-NIL did not alter blood pressure or blood flow in any of the groups. iNOS and eNOS mRNA increased in both colitis models, whereas nNOS remained at the control level. TNBS- and DSS-induced colitis results in increased colonic mucosal blood flow, most probably due to increased eNOS activity.


1995 ◽  
Vol 268 (2) ◽  
pp. H569-H575 ◽  
Author(s):  
S. C. Jones ◽  
J. L. Williams ◽  
M. Shea ◽  
K. A. Easley ◽  
D. Wei

Cycling of various cerebral metabolic substances, arterial vascular diameter, and flow has been noted by many workers at a frequency near 0.1 Hz. Suspicion that this phenomenon is dependent on the type of anesthesia led us to investigate the occurrence of cerebral blood flow (CBF) cycling with different anesthetics. Fifteen Sprague-Dawley rats were anesthetized with either pentobarbital (n = 5, 40–50 mg/kg), alpha-chloralose (n = 5, 60 mg/kg), or halothane (n = 5, 1–0.5%). Body temperature was maintained at 37 degrees C. Femoral arterial and venous catheters were placed, and a tracheotomy was performed, permitting artificial ventilation with 30% O2–70% N2. A closed cranial window was formed over a 3-mm diameter craniotomy. Mean arterial pressure (MABP), arterial partial pressures of CO2 and O2 (PaCO2 and PaO2), and pH were controlled and stabilized at normal values. CBF was determined using laser Doppler flowmetry. To induce cycling, MABP was transiently and repeatedly lowered by exsanguination. Fast Fourier analysis of selected 64-s flow recordings (n = 38) was performed. CBF cycling was observed, independent of the type of anesthesia, in all animals. In 36 epochs, cycling was induced when MABP was reduced to a mean pressure of 65 +/- 1.5 mmHg. The mean frequency and amplitude were 0.094 +/- 0.003 Hz and 6.6 +/- 0.5%, respectively. Cycling occurred without blood withdrawal in two epochs. With the use of the blood-withdrawal epochs (n = 36), all three anesthetics shared a common linear slope between amplitude and blood pressure (P < 0.02) and blood pressure change (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


1991 ◽  
Vol 11 (5) ◽  
pp. 861-867 ◽  
Author(s):  
Christer Nilsson ◽  
Maria Lindvall-Axelsson ◽  
Christer Owman

Using laser-Doppler flowmetry during ventriculocisternal perfusion with inulin-[14C]carboxylic acid, choroid plexus blood flow (CPBF) and CSF production were measured simultaneously in rats during periods of 3 h. Blood flow and CSF production decreased only slightly during control experiments. The effect of vasoactive intestinal polypeptide (VIP) was studied at different concentrations of the peptide given either intraventricularly or intravenously. Intraventricular administration of VIP (10−9 or 10−7 M) resulted in a decrease in CSF production of up to 30%, while CPBF increased by 20%, also demonstrating that CSF production and blood flow are not directly coupled in the choroid plexus. When infused intravenously, VIP (10 or 100 pmol/kg/min) increased CPBF, an effect partly antagonized at higher concentrations owing to a VIP-induced systemic hypotension. No effect of VIP on CSF production could be seen with intravenous administration.


Neurosurgery ◽  
1989 ◽  
Vol 24 (2) ◽  
pp. 166-170 ◽  
Author(s):  
E. Arbit ◽  
G. R. DiResta ◽  
R. F. Bedford ◽  
N. K. Shah ◽  
J. H. Galicich

Abstract A new technique, laser-Doppler flowmetry, has been used intraoperatively to measure blood flow responses in normal brain tissue and brain tumor to blood pressure and arterial blood gas alterations. We have observed that blood flow is reduced in most cerebral tumors, and that most tumors retain the normal response to changes in arterial blood gas; however, these responses are varied. One group of tumors in our study demonstrated an autoregulatory capacity; a second behaved passively—that is, blood flow changes followed blood pressure—while a third showed no response.


1984 ◽  
Vol 246 (2) ◽  
pp. G195-G203
Author(s):  
R. H. Gallavan ◽  
Y. Tsuchiya ◽  
E. D. Jacobson

The purpose of this study was to determine the effects of nicotine on intestinal blood flow and oxygen consumption. The intravenous infusion of nicotine at doses corresponding to those experienced by smokers produced a transient increase in systemic arterial blood pressure and mesenteric blood flow. Subsequently a steady-state response developed that consisted of a reduction in mesenteric blood flow due to both a decrease in blood pressure and an increase in intestinal vascular resistance. This increase in resistance was probably due to increased levels of circulating catecholamines. The intra-arterial infusion of nicotine into the intestinal circulation at doses experienced by the average smoker had no effect on either intestinal blood flow or oxygen consumption. Similarly, under in vitro conditions nicotine had no direct effect on intestinal vascular smooth muscle tension. Thus, nicotine appears to reduce intestinal blood flow indirectly as a result of its systemic effects.


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