The Actions of Nitrovasodilators on Spontaneously Active Smooth Muscle

Smith, Andrew David (1994) The Actions of Nitrovasodilators on Spontaneously Active Smooth Muscle. PhD thesis, University of Glasgow.

Full text available as:
[img]
Preview
PDF
Download (6MB) | Preview

Abstract

1. The aim of this study was to investigate the actions of nitric oxide (NO) donors i.e. nitrovasodilators, on the extracellular electrical and mechanical activity recorded from spontaneously active smooth muscle, in particular the rabbit distal colon (RDC), rabbit portal vein (RPV) and rat portal vein (rat PV), in vitro, using the Golenhofen apparatus. First, circular strips of RDC were examined for evidence of a "nitrergic" innervation. 2. Addition of carbachol (3 x 10-5M) to circular strips of RDC mounted in a conventional (25m1) organ bath raised the tone to 7.73 +/- 0.67g (n = 44). Electrical stimulation (16 pulses, 1-16Hz, 0.1-0.5ms, supramaximal voltage), in the presence of phentolamine and propranolol (each 3 x 10-6M), produced frequency-dependent, non-adrenergic, non-cholinergic (NANC) nerve-mediated relaxations and rebound contractions. 3. NANC relaxations induced by nerve stimulation were mimicked by authentic NO (≥10-5M), and partially inhibited by the avid NO binding molecule, haemoglobin (Hb; 3 x 10-5M), or by the inhibitor of endogenous NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME ; 5 x 10-4M). On some occasions, L-NAME-induced inhibition was reversed by the precursor to NO synthesis, L-arginine. The response to authentic NO (2 x 10-5M) was abolished by Hb (3 x 10-5M). 4. Rebound contractions in response to inhibitory NANC nerve stimulation were mimicked by authentic NO (≥10-5M) and partially inhibited by L-NAME (5 x 10-4M) or the cyclooxygenase inhibitor, indomethacin (10-5M). 5. Unstretched, longitudinal strips of RDC mounted in the Golenhofen apparatus exhibited spontaneous, calcium-dependent spike bursts that were always accompanied by contraction. The frequency and duration of these electrical events was 3.77 +/- 0.18 bursts min-1 (n = 80) and 7.91 +/- 0.77s (n = 57) respectively, and each contained 7.84 +/- 0.62 spikes (n = 61). The amplitude of the largest spike in each was 248.46 +/- 28.37 muV (n = 63) while the amplitude of corresponding contraction was 2.21 +/- 0.13g (n = 79). Contractile bursts lasted for 12.23 +/- 1.42s (n = 79) and each contained 2.78 +/- 0.33 mechanical peaks (n = 79). 6. Under an applied tension of 1g, intact sections of RPV mounted in the Golenhofen apparatus exhibited spontaneous spike bursts that were always accompanied by contraction. The frequency and duration of electrical events was 2.95 +/- 0.41 bursts min-1 (n = 5) and 7.40 +/- 1.94s (11= 4) respectively, and each contained 16.76 +/- 3.14 spikes (n = 4). The amplitude of the largest spike in each was 24.67 +/- 2.60 muV (n = 3) while the amplitude of corresponding contraction, including the 1g applied, was 1.59 +/- 0.2g (n = 5). Contractile bursts lasted for 12.17 +/- 1.57s (n = 5) and each contained 1.50 +/- 0.2 mechanical peaks (n = 5). 7. Under an applied tension of 1g, intact sections of rat PV mounted in the Golenhofen apparatus exhibited spontaneous, calcium-dependent spike bursts, that were always accompanied by contraction. The frequency and duration of electrical events was 2.61 +/- 0.14 bursts min-1 (n = 49) and 6.81 +/- 0.56s (n = 24) respectively, and each contained 15.08 +/- 1.11 spikes (n = 20). The amplitude of the largest spike in each was 39.04 +/- 3.69 muV (n = 24) while the amplitude of corresponding contraction, including the 1g applied, was 1.48 +/- 0.39g (n = 49). Contractile bursts lasted for 8.31 +/- 0.36s (n = 49) and each contained 1.63 +/- 0.08 mechanical peaks (n = 49). 8. Nitrovasodilators in the form of sodium nitroprusside (SNP), glyceryl trinitrate (GTN) or isosorbide dinitrate (IDN), each possessed both inhibitory and excitatory properties in the RDC. SNP was the most effective and, consequently, was used as a model for this group of drugs. Each nitrovasodilator (≥10-5M) induced a short-lived period of quiescence in unstretched, longitudinal strips of RDC. Following this, an altered pattern of spontaneous electrical and mechanical activity returned abruptly. In tissues with a low initial frequency (< 6 bursts min-1), SNP or IDN (each ≥10-5M) significantly enhanced the frequency of activity. In tissues with a high initial frequency (> 6 bursts min-1), SNP (10-5M) significantly reduced the frequency of activity. Spike amplitude was increased significantly by GTN (10-6M) and, on occasion, by SNP (≥10-5M), while the number of spikes per burst and the duration of each burst were reduced significantly by SNP (?10-5M) or IDN (≥10-5M and 10-4M respectively). Only SNP (≥10-5M) significntly reduced the number of mechanical peaks per burst but both SNP (≥10-6M) and IDN (?10-5M) significantly decreased the duration of mechanical events. Each of the nitrovasodilators (each ≥10-5M) significantly lowered the amplitude of spontaneous contraction.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: T C Muir
Keywords: Pharmacology
Date of Award: 1994
Depositing User: Enlighten Team
Unique ID: glathesis:1994-75665
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 18:59
Last Modified: 19 Nov 2019 18:59
URI: http://theses.gla.ac.uk/id/eprint/75665

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year