Role of Substance P in the Vascular Response of Nasal Mucosa in Nasal Allergy

1996 ◽  
Vol 105 (8) ◽  
pp. 648-653 ◽  
Author(s):  
Akiyoshi Konno ◽  
Toyoyuki Hanazawa ◽  
Tsutomu Numata ◽  
Hiroshi Nagata ◽  
Nobuhisa Terada ◽  
...  
Keyword(s):  
Blood Flow ◽  
Substance P ◽  
Sensory Stimulation ◽  
Nasal Allergy ◽  
Vascular Response ◽  
Nasal Challenge ◽  
C Fiber ◽  
Capacitance Vessels ◽  
Dose Dependent

The effects of topically administered substance P (SP) on nasal blood flow and nasal airway resistance (NAR) were evaluated in 11 subjects with perennial nasal allergy. The change in NAR induced by SP was compared with those induced by nasal challenge with histamine, leukotriene EM (LTD4), and antigen. In doses ⩾ 16 nmol, SP caused a significant increase of nasal blood flow within 5 minutes that lasted for less than 20 minutes. In doses ⩾16 nmol, SP caused a dose-dependent, short-lasting, significant increase in NAR. The magnitude of the increase in NAR was LTD4 > SP > histamine when compared on a molar basis. Our results may suggest that SP released from C fiber terminals is partially involved in an early nasal vascular response after antigen challenge by acting on adjacent vascular smooth muscle to cause a transient vasodilatation of both resistance and capacitance vessels only while sensory stimulation persists in subjects with nasal allergy.

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

1997 ◽  
Vol 92 (2) ◽  
pp. 123-131 ◽  
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.

PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs

1997 ◽  
Vol 272 (6) ◽  
pp. L1066-L1069
Author(s):  
H. Kanazawa ◽  
H. Kamoi ◽  
T. Kawaguchi ◽  
S. Shoji ◽  
T. Fujii ◽  
...  
Keyword(s):  
Substance P ◽  
Bronchoalveolar Lavage ◽  
Guinea Pigs ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Neurokinin A ◽  
Dependent Manner ◽  
C Fiber ◽  
Dose Dependent

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.

Postprandial intestinal hyperemia: role of bile salts in the ileum

1981 ◽  
Vol 241 (6) ◽  
pp. G469-G477 ◽  
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.

Assessment of microvascular endothelial function in human skin

2001 ◽  
Vol 101 (6) ◽  
pp. 567-572 ◽  
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.

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

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
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.

Vasodilation induced by endothelin: role of EDRF and prostanoids in rat hindquarters

1990 ◽  
Vol 259 (6) ◽  
pp. H1835-H1841 ◽  
Author(s):  
E. H. Ohlstein ◽  
L. Vickery ◽  
C. Sauermelch ◽  
R. N. Willette
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Perfusion Pressure ◽  
Microvascular Perfusion ◽  
Hemodynamic Effects ◽  
Hemodynamic Responses ◽  
Pithed Rats ◽  
Dose Dependent

Hemodynamic responses to endothelin (ET-1) were studied in hindquarters of anesthetized rats and also in isolated buffer-perfused hindquarters of pithed rats. ET-1 (10-100 pmol ia) produced brief dose-related increases in hindquarter blood flow. Acetylcholine (ACh. 0.3-1 micrograms ia) produced similar vasodilator responses. Hemodynamic responses elicited by either ET-1 or ACh were not significantly altered by pretreatment with indomethacin. ET-1 produced dose-dependent increases in skeletal muscle microvascular perfusion, whereas ET-1 had no effect on cutaneous microvascular perfusion, suggesting that vasodilation in the skeletal muscle of the hindlimb contributes to the increase in hindquarter blood flow induced by ET-1. Hemodynamic effects of ET-1 and ACh were studied in the isolated in situ buffer-perfused hindquarters of pithed rats. ET-1 (0.01-300 pmol ia) produced only dose-dependent increases in hindquarter perfusion pressure under basal conditions or when the vascular preparation was precontracted with methoxamine. ET-1 induced vasorelaxation was not observed. ACh (3 microgram ia) produced a 64% reduction in hindquarter perfusion pressure; indicative of endothelium-dependent relaxation. ET-3 (0.1-300 pmol) produced only dose-dependent increases in hindquarter perfusion pressure. When hemodynamic effects of ET-1 were studied under conditions of constant pressure, results were similar to those obtained under constant flow. This study demonstrates that in the rat hindquarters endothelium-derived relaxing factors and prostanoids do not appear to be mediators of endothelin-induced vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostanoids in regulation of postprandial jejunal hyperemia and oxygen uptake

1989 ◽  
Vol 257 (5) ◽  
pp. G798-G808 ◽  
Author(s):  
C. C. Chou ◽  
A. Alemayehu ◽  
M. J. Mangino
Keyword(s):  
Blood Flow ◽  
Thromboxane A2 ◽  
Prostaglandin I2 ◽  
O2 Uptake ◽  
Blood Concentrations ◽  
Anesthetized Dogs ◽  
Txa2 Receptor ◽  
Txa2 Receptor Antagonist ◽  
Dose Dependent

The role of prostanoids in regulation of jejunal blood flow (JBF) was studied in anesthetized dogs. Intra-arterial infusions of arachidonate produced biphasic changes and dose-dependent decreases in jejunal vascular resistance (JVR) in untreated and aspirin-pretreated dogs, respectively; mefenamate abolished these responses. The jejunum released prostaglandin I2 (PGI2) greater than PGE2 greater than thromboxane A2 (TXA2) (radioimmunoassay) under resting conditions, and food enhanced the release of PGE2 greater than PGI2 greater than TXA2 greater than PGF2 alpha. Addition of arachidonate to food enhanced TXA2 and PGF2 alpha releases and decreased PGI2 and PGE2 releases, while inhibiting the food-induced increases in JBF and O2 uptake; mefenamate inhibited these arachidonate actions. A TXA2 receptor antagonist (SQ-29548) reversed the arachidonate vascular and metabolic actions. Intra-arterial infusions of PGI2 or PGE2 decreased, whereas TXA2 analogue U-44069 or PGF2 alpha increased JVR. A mixture of these prostanoids infused at blood concentrations similar to the increase observed during food placement did not alter JVR. At concentrations similar to the increases observed when arachidonate was added to luminal food, the infusions increased JVR and abolished the food-induced decrease in JVR. In conclusion, jejunal productions of PGI2, PGE2, TXA2, and PGF2 alpha increase during nutrient absorption. Addition of arachidonate to food attenuates the former two and enhances the latter two releases, which act to attenuate food-induced jejunal hyperemia.

Role of perivascular nerve and sensory neurotransmitter dysfunction in inflammatory bowel disease

2021 ◽  
Author(s):  
Charles E. Norton ◽  
Elizabeth A. Grunz-Borgmann ◽  
Marcia L. Hart ◽  
Benjamin W. Jones ◽  
Craig L. Franklin ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Blood Flow ◽  
Substance P ◽  
Bowel Disease ◽  
Vascular Dysfunction ◽  
Receptor Expression ◽  
Mesenteric Arteries ◽  
Increased Risk ◽  
Inflammatory Bowel

Inflammatory Bowel Disease (IBD) is associated with both impaired intestinal blood flow and increased risk of cardiovascular disease, but the functional role of perivascular nerves that control vasomotor function of mesenteric arteries (MAs) perfusing the intestine during IBD is unknown. Because perivascular sensory nerves and their transmitters calcitonin gene-related peptide (CGRP) and substance P (SP) are important mediators of both vasodilation and inflammatory responses, our objective was to identify IBD-related deficits in perivascular sensory nerve function and vascular neurotransmitter signaling. In MAs from an IL-10-/- mouse model, IBD significantly impairs electrical field stimulation (EFS)-mediated sensory vasodilation and inhibition of sympathetic vasoconstriction, despite decreased sympathetic nerve density and vasoconstriction. The MA content and EFS-mediated release of both CGRP and SP are decreased with IBD, but IBD has unique effects on each transmitter. CGRP nerve density, receptor expression, hyperpolarization and vasodilation are preserved with IBD. In contrast, SP nerve density and receptor expression are increased, and SP hyperpolarization and vasodilation are impaired with IBD. A key finding is that blockade of SP receptors restores EFS-mediated sensory vasodilation and enhanced CGRP-mediated vasodilation in MAs from IBD but not Control mice. Together, these data suggest that an aberrant role for the perivascular sensory neurotransmitter SP and its downstream signaling in MAs underlies vascular dysfunction with IBD. We propose that with IBD, SP signaling impedes CGRP-mediated sensory vasodilation, contributing to impaired blood flow. Thus, substance P and NK1 receptors may represent an important target for treating vascular dysfunction in IBD.

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