Arginine vasopressin reduces intestinal oxygen supply and mucosal tissue oxygen tension

We investigated intestinal oxygen supply and mucosal tissue Po2during administration of increasing dosages of continuously infused arginine vasopressin (AVP) in an autoperfused, innervated jejunal segments in anesthetized pigs. Mucosal tissue Po2was measured by employing two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular hemoglobin was determined by tissue reflectance spectrophotometry. Microvascular blood flow was assessed by laser-Doppler velocimetry. Systemic hemodynamic variables, mesenteric venous and systemic acid-base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline and at 20-min intervals during incremental AVP infusion ( n = 8; 0.007, 0.014, 0.029, 0.057, 0.114, and 0.229 IU·kg−1·h−1, respectively) or infusion of saline ( n = 8). AVP infusion led to a significant ( P < .05), dose-dependent decrease in cardiac index (from 121 ± 31 to 77 ± 27 ml·kg−1·min−1at 0.229 IU·kg−1·h−1) and systemic oxygen delivery (from 14 ± 3 to 9 ± 3 ml·kg−1·min−1at 0.229 IU·kg−1·h−1) concomitant with an increase in systemic oxygen extraction ratio (from 31 ± 4 to 48 ± 10%). AVP decreased microvascular blood flow (from 133 ± 47 to 82 ± 35 perfusion units at 0.114 IU·kg−1·h−1), mucosal tissue Po2(from 26 ± 7 to 7 ± 2 mmHg at 0.229 IU·kg−1·h−1), and microvascular hemoglobin oxygen saturation (from 51 ± 9 to 26 ± 12% at 0.229 IU·kg−1·h−1) without a significant increase in mesenteric venous lactate concentration (2.3 ± 0.8 vs. 3.4 ± 0.7 mmol/l). We conclude that continuously infused AVP decreases intestinal oxygen supply and mucosal tissue Po2due to a reduction in microvascular blood flow and due to the special vascular supply in the jejunal mucosa in a dose-dependent manner in pigs.

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Effects of Endothelin on Systemic and Renal Haemodynamics and Neuroendocrine Hormones in Conscious Dogs

Clinical Science ◽

10.1042/cs0770567 ◽

1989 ◽

Vol 77 (5) ◽

pp. 567-572 ◽

Cited By ~ 29

Author(s):

Hidetomo Nakamoto ◽

Hiromichi Suzuki ◽

Marohito Murakami ◽

Yo Kageyama ◽

Akira Ohishi ◽

...

Keyword(s):

Blood Flow ◽

Plasma Renin Activity ◽

Renal Blood Flow ◽

Arginine Vasopressin ◽

Adrenocorticotropic Hormone ◽

Bolus Injection ◽

Plasma Renin ◽

Peak Level ◽

Dependent Manner ◽

Dose Dependent

1. The effects of endothelin on systemic and renal haemodynamics and plasma concentrations of neuroendocrine hormones including plasma renin activity, aldosterone, adrenocorticotropic hormone, Cortisol, catecholamines and arginine vasopressin were investigated in 18 conscious dogs. 2. Bolus injection of 4 pmol of endothelin/kg did not cause any significant changes in haemodynamics. Mean arterial pressure was elevated by both doses of 40 pmol/kg [91 ± 2 to 99 ± 2 mmHg (12.1 ± 0.3 to 13.2 ± 0.3 kPa), P < 0.05] or 200 pmol/kg [93 ± 2 to 107 ± 3 mmHg (12.4 ± 0.3 to 14.3± 0.4 kPa), P < 0.01], the latter dose increasing cardiac output (14%, P < 0.05) and heart rate (9%, P < 0.05), and the former reducing these parameters (14% and 8%, P < 0.05, respectively). 3. In contrast with the various changes in systemic haemodynamics, renal blood flow transiently increased immediately after bolus injection in a dose-dependent manner (28%, P < 0.05, 50%, P < 0.01 and 110%, P < 0.01 with 4, 40 and 200 pmol of endothelin/kg, respectively). This transient elevation of renal blood flow was followed by a gradual decrease (16%, P < 0.05; 31%, P < 0.01 and 36%, P < 0.01) at 10 min. 4. All neurohormones were elevated in a dose-dependent manner. 5. Among these hormones, arginine vasopressin and plasma renin activity reached a peak level at 5 min (from 2.21 ± 0.45 to 6.37 ± 0.60 pmol/l, P < 0.01, and from 0.65 ± 0.08 to 1.09 ± 0.10 pmol of angiotensin 1 h−1 ml−1P < 0.01, respectively) after bolus injection of 200 pmol of endothelin/kg, whereas adrenocorticotropic hormone and Cortisol reached a peak level at 15 min (from 6.0 ± 0.7 to 18.2 ± 1.5 pmol/l, P < 0.01, and from 4.4 ± 0.9 to 16.5 ± 2.7 × 10−2 μmol/l, P < 0.01, respectively). 6. These results suggest that endothelin is a potent vasoconstrictive peptide in vivo with a marked effect on the renal vascular system, and that it induces elevation of vasoactive hormones directly and/or through central effects.

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Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650532 ◽

1996 ◽

Vol 76 (01) ◽

pp. 111-117 ◽

Cited By ~ 10

Author(s):

Yasuto Sasaki ◽

Junji Seki ◽

John C Giddings ◽

Junichiro Yamamoto

Keyword(s):

Blood Flow ◽

Thrombus Formation ◽

Dependent Manner ◽

Red Cell ◽

Cell Velocity ◽

Red Cell Velocity ◽

The Mean ◽

Wall Shear ◽

Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

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Blockade of Cerebral Blood Flow Response to Insulin-Induced Hypoglycemia by Caffeine and Glibenclamide in Conscious Rats

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199712000-00006 ◽

1997 ◽

Vol 17 (12) ◽

pp. 1309-1318 ◽

Cited By ~ 25

Author(s):

Naoaki Horinaka ◽

Tang-Yong Kuang ◽

Hazel Pak ◽

Robert Wang ◽

Jane Jehle ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Degradation Products ◽

Dependent Manner ◽

Conscious Rats ◽

Intravenous Injections ◽

Adenosine Receptor Antagonist ◽

Flow Response ◽

Arterial Plasma ◽

Dose Dependent

The possibility that adenosine and ATP-sensitive potassium channels (KATP) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 μmol/L glibenclamide, a KATP channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats ( P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia ( P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 μmol/L glibenclamide, and almost complete blockade (+5%) with 2 μmol/L glibenclamide. These results suggest that adenosine and KATP channels may play a role in the increases in CBF during hypoglycemia.

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Postprandial intestinal hyperemia: role of bile salts in the ileum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1981.241.6.g469 ◽

1981 ◽

Vol 241 (6) ◽

pp. G469-G477 ◽

Cited By ~ 5

Author(s):

P. R. Kvietys ◽

J. M. McLendon ◽

D. N. Granger

Keyword(s):

Blood Flow ◽

Oxygen Uptake ◽

Bile Salt ◽

Bile Salts ◽

Dependent Manner ◽

Salt Solutions ◽

Dose Dependent ◽

Oxygen Difference ◽

Artificial Pressure

In an autoperfused dog ileum preparation, artificial pressure, venous outflow pressure, blood flow, and arteriovenous oxygen difference were measured while bile and bile salt solutions, at physiological concentrations, were placed in the lumen. Intraluminal placement of endogenous bile, synthetic bile, or bile salt solutions increased ileal blood flow (99 +/- 10, 94 +/- 20, and 104 +/- 17%, respectively) and oxygen uptake (30 +/- 5, 36 +/- 9, and 28 +/- 5%, respectively). Endogenous bile pretreated with cholestyramine, a bile salt-sequestering resin, did not alter ileal blood flow, yet increased ileal oxygen uptake by 11 +/- 3%, a response similar to that observed while Tyrode's solution (the vehicle) was in the lumen. Intra-arterial infusion of bile salts increased ileal blood flow in a dose-dependent manner, while not significantly altering ileal oxygen uptake. The results of the present study indicate that bile salts play an important role in the functional (postprandial) hyperemia in the ileum by 1) directly dilating the ileal vasculature and 2) enhancing ileal metabolism during their active absorption.

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Role of Nitric Oxide towards Vasodilator Effects of Substance P and ATP in Human Forearm Vessels

Clinical Science ◽

10.1042/cs0920123 ◽

1997 ◽

Vol 92 (2) ◽

pp. 123-131 ◽

Cited By ~ 18

Author(s):

Masanari Shiramoto ◽

Tsutomu Imaizumi ◽

Yoshitaka Hirooka ◽

Toyonari Endo ◽

Takashi Namba ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Substance P ◽

Sodium Nitroprusside ◽

Forearm Blood Flow ◽

Dependent Manner ◽

Human Forearm ◽

Before And After ◽

Dose Dependent

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-l-arginine (4 or 8 μmol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of l-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-l-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of l-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

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Assessment of microvascular endothelial function in human skin

Clinical Science ◽

10.1042/cs1010567 ◽

2001 ◽

Vol 101 (6) ◽

pp. 567-572 ◽

Cited By ~ 34

Author(s):

David J. NEWTON ◽

Faisel KHAN ◽

Jill J.F. BELCH

Keyword(s):

Blood Flow ◽

Substance P ◽

Endothelial Function ◽

Animal Studies ◽

Doppler Imaging ◽

Microvascular Blood Flow ◽

Coefficients Of Variation ◽

Forearm Skin ◽

Invasive Techniques ◽

Dose Dependent

Endothelial dysfunction is an important factor in many cardiovascular diseases, and is commonly associated with impaired endothelium-mediated vasodilatation. Information about the mechanisms behind this dysfunction has come largely from animal studies or, in humans, through invasive techniques that are not specific to one vascular bed. We have developed protocols to assess endothelial function non-invasively in the cutaneous microcirculation by measuring blood flow responses to four receptor-specific vasoactive compounds. Cumulative doses of acetylcholine, methacholine, bradykinin and substance P were administered iontophoretically to the forearm skin of healthy volunteers on two to three occasions. Dose-dependent increases in skin microvascular blood flow in response to these drugs were measured with laser Doppler imaging. Vascular responses to acetylcholine and methacholine were reasonably consistent, with coefficients of variation of approx. 17%. The coefficients of variation for bradykinin and substance P were much poorer, as high as 70% for some doses. This might partly be a consequence of the more unpredictable effects of histamine release in the vasoactive behaviour of these two agonists. Although it might be advantageous to find other agonists with which to test the function of different receptor pathways, we have shown that just acetylcholine and methacholine can currently be used with iontophoresis to allow sensitive and reproducible assessment of endothelial function.

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Microvascular hematocrit and red cell flow in resting and contracting striated muscle

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1979.237.4.h481 ◽

1979 ◽

Vol 237 (4) ◽

pp. H481-H490 ◽

Cited By ~ 69

Author(s):

B. Klitzman ◽

B. R. Duling

Keyword(s):

Blood Flow ◽

Oxygen Supply ◽

Striated Muscle ◽

Volume Fraction ◽

Plasma Layer ◽

Element Model ◽

Microvascular Blood Flow ◽

Red Cell ◽

Total Blood ◽

Arterial Blood

Microvascular hematocrit and its possible relation to oxygen supply were systematically examined. We studied the red cell volume fraction (hematocrit) in arterial blood and in capillaries under a variety of circumstances. Control capillary hematocrit averaged 10.4 +/- 2.0% (SE) and arteriolar (14.2 micrometer ID) hematocrit averaged 13.9 +/- 1.2% in cremaster muscles of pentobarbital-anesthetized hamsters. Carotid artery hematocrit was 53.2 +/- 0.6%. The low microvessel hematocrit could not be entirely explained by a high red cell flux through arteriovenous channels other than capillaries (shunting). Hematocrit was not only low at rest, but varied with physiological stimuli. A 1-Hz muscle contraction increased capillary hematocrit to 18.5 +/- 2.4%, and maximal vasodilation induced a rise to 39.3 +/- 9.5%. The quantitative relations between capillary red cell flux, arterial hematocrit, and total blood flow could be explained by a two-element model of microvascular blood flow that incorporated a relatively slow-moving plasma layer (1.2 micrometer). Such a model would generate a low microvessel hematocrit and might reduce the diffusion capacity of individual capillaries, but would not reduce time-averaged red cell flux or alter steady-state vascular oxygen supply.

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Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats

Advances in Pharmacological Sciences ◽

10.1155/2015/801053 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Aghdas Dehghani ◽

Shadan Saberi ◽

Mehdi Nematbakhsh

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Wistar Rats ◽

Group Versus ◽

Dependent Manner ◽

Mas Receptor ◽

Flow Response ◽

Renal Vascular ◽

Dose Dependent

Background. The accompanied role of Mas receptor (MasR), bradykinin (BK), and female sex hormone on renal blood flow (RBF) response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779) and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats.Methods. Ovariectomized Wistar rats received estradiol (OVE) or vehicle (OV) for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP), RBF, and renal vascular resistance (RVR) responses to Ang 1-7 (0, 100, and 300 ng kg−1 min−1) were determined.Results. Percentage change of RBF (%RBF) in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P<0.05). Infusion of 300 ng kg−1 min−1Ang 1-7 increased RBF by6.9±1.9% in OVE group versus0.9±1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly.Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.

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