Effect of neuropeptides released from sensory nerves on blood flow in the rat airway microcirculation

1992 ◽  
Vol 72 (4) ◽  
pp. 1563-1570 ◽  
Author(s):  
G. Piedimonte ◽  
J. I. Hoffman ◽  
W. K. Husseini ◽  
W. L. Hiser ◽  
J. A. Nadel

Stimulation of sensory nerves in the airway mucosa causes local release of the neuropeptides substance P and calcitonin gene-related peptide (CGRP). In this study we used a modification of the reference-sample microsphere technique to measure changes in regional blood flow and cardiac output distribution produced in the rat by substance P, CGRP, and capsaicin (a drug that releases endogenous neuropeptides from sensory nerves). Three sets of microspheres labeled with different radionuclides were injected into the left ventricle of anesthetized F344 rats before, immediately after, and 5 min after left ventricular injections of capsaicin, substance P, or CGRP. The reference blood sample was withdrawn from the abdominal aorta and was simultaneously replaced with 0.9% NaCl at 37 degrees C. We found that stimulation of sensory nerves with a low dose of capsaicin causes a large and selective increase in microvascular blood flow in the extrapulmonary airways. The effect of capsaicin is mimicked by systemic injection of substance P but not by CGRP, suggesting that substance P is the main agent of neurogenic vasodilation in rat airways.

1982 ◽  
Vol 52 (6) ◽  
pp. 1629-1635 ◽  
Author(s):  
M. H. Laughlin ◽  
R. B. Armstrong ◽  
J. White ◽  
K. Rouk

A catheter-implantation procedure allowing use of the radiolabeled microsphere (MS) technique for measuring skeletal muscle blood flow (BF) in rats during high-speed treadmill running was desired. Attempts to use existing procedures were unsuccessful. We found that Silastic catheters (0.02 in. ID X 0.037 in. OD) placed in the ascending aorta (for MS infusions) and the renal artery (for reference sample withdrawal) minimized these exercise performance problems. It was then necessary to establish that aortic MS infusions result in good MS-blood mixing. We tested the method with the following: 1) the radioactivities found in reference withdrawal samples taken from two locations in the aorta were compared after left ventricular (LV) infusion and after aortic infusion; 2) BFs to bilaterally paired tissues were compared in anesthetized and conscious rats with LV and aortic infusions; 3) the distribution of MSs in the muscles was studied histologically; and 4) BFs in bilaterally paired tissues were compared in rats with aortic MS infusions during treadmill running. The results indicate that 1) the percent difference between the radioactivities found in the proximal and distal reference withdraw samples was the same for LV and aortic MS infusions; 2) BF to bilaterally paired tissue samples was the same with both LV or aortic MS infusions; 3) the MSs were distributed uniformly within muscles, and MS aggregation was not a significant problem; and 4) BFs to bilaterally paired tissue samples were the same in exercising rats. We conclude that this technique can be used to measure muscle BF in rats running on a treadmill.


1995 ◽  
Vol 268 (3) ◽  
pp. H1202-H1207
Author(s):  
A. Roitstein ◽  
B. V. Cheinberg ◽  
J. Kedem ◽  
J. Tse ◽  
H. R. Weiss ◽  
...  

In a dog model of left ventricular hypertrophy (LVH) created by aortic valve plication, we examined the hypothesis that regional myocardial inotropic and metabolic responses to alpha-adrenergic stimulation would be diminished due to decreased alpha-adrenoceptor number. After systemic beta-adrenergic blockade, phenylephrine (PE, 5 micrograms.kg-1.min-1) was infused into the left anterior descending artery in eight LVH and nine control open-chest anesthetized dogs. The circumflex region served as control. In both regions, local segment work was calculated as the integrated products of force (miniature transducer) and segment shortening (ultrasonic crystals). Local myocardial O2 consumption was calculated from regional blood flow (microspheres) and O2 saturation (microspectrophotometry). A saturation radioligand binding assay was used to determine adrenoceptor number and affinity. In control animals in the treated region, PE increased work from 815 +/- 140 to 1,493 +/- 149 g.mm.min-1. In LVH, work was not significantly altered (688 +/- 142 vs. 730 +/- 149 g.mm.min-1). Regional blood flow was elevated in controls (81 +/- 10 to 141 +/- 24 ml.min-1.100 g-1) but was not changed in LVH (105 +/- 12 vs. 123 +/- 18 ml.min-1.100 g-1). In controls, but not in LVH, myocardial O2 consumption was almost doubled during PE infusion (6.2 +/- 0.9 vs. 12.0 +/- 2.1 ml O2.min-1.100 g-1). alpha-Adrenoceptor number and dissociation constants values were not different between control and LVH (15.7 +/- 2.8 vs. 16.4 +/- 2.7 fmol/mg protein; 13.2 +/- 3.4 vs. 16.9 +/- 4.3 nm, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


1978 ◽  
Vol 235 (4) ◽  
pp. H445-H451 ◽  

Previous studies from this laboratory have indicated an important role for angiotensin-sensitive anteroventral third ventricular (AV3V) brain structures in normal regulation of arterial pressure and development of renal hypertension. The present experiments examined the effects of electrical stimulation of these periventricular areas on arterial pressure and regional blood flow in the anesthetized rat. Electrodes were placed in the AV3V region 3–10 days prior to acute studies. Blood flow was measured in extracorporeal blood flow circuits. Electrical stimulation produced only small changes in arterial pressure. Despite the small pressure changes, stimulation caused marked frequency-dependent alterations in regional blood flow. Renal and splanchnic flows were reduced while hindlimb flow was increased. Resistance changes were abolished by surgical denervation or ganglionic blockade but were unaffected by adrenalectomy. Hemodynamic responses to AV3V stimulation were abolished by a lesion in the area of the median eminence. It may be concluded that AV3V stimulation, through activation of pathways descending through the ventromedial hypothalamus-median eminence region, produces profound regional blood flow shifts without greatly altering arterial pressure.


1986 ◽  
Vol 64 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Tony G. Waldrop ◽  
Mark C. Henderson ◽  
Gary A. Iwamoto ◽  
Jere H. Mitchell

2001 ◽  
Vol 101 (6) ◽  
pp. 567-572 ◽  
Author(s):  
David J. NEWTON ◽  
Faisel KHAN ◽  
Jill J.F. BELCH

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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