Differences in cardiovascular responses to peripherally administered GABA as influenced by basal conditions and type of anaesthesia

Abstract

1 The cardiovascular (blood pressure, heart rate, cardiac contractility) effects of i.v. -y-aminobutyric acid (GABA) were investigated in guinea-pigs anaesthetized with barbitone or urethane. 2 GABA (0.1-10mgkg-') produced a transient 'depressive' effect on cardiovascular parameters which in barbitone-anaesthetized animals was followed by a transient 'excitatory' effect. Resting cardiovascular parameters were higher in urethane-as compared to barbitone-anaesthetized animals. 3 Picrotoxin pretreatment (2 mg kg-, i.v.) barely affected the cardiovascular changes produced by GABA in barbitone-anaesthetized animals. In picrotoxin pretreated animals anaesthetized with urethane, GABA produced an initial depression of cardiovascular parameters followed by an excitatory phase. 4 Hexamethonium (20 mg kg-', i.v) suppressed or reduced markedly the GABA-induced cardiovascular changes both in barbitone-or urethane-anaesthetized animals. 5 Reserpine pretreatment lowered resting cardiovascular parameters. In these animals, regardless of type of anaesthesia, the effects of i.v. GABA were of the 'excitatory' type only. Reserpine pretreated animals anaesthetized with barbitone were selected for further experiments. 6 Various GABAA receptor agonists (homotaurine, muscimol, THIP, 5-aminovaleric acid) mimicked the 'excitatory' effect of GABA in reserpine pretreated animals anaesthetized with barbitone and prevented the effects of subsequent GABA administration. On the other hand (±)-baclofen, a selective GABAB receptor agonist, had a slight depressant effect and did not prevent the 'excitatory' cardiovascular effects of GABA. 7 Neither bicuculline nor picrotoxin pretreatment prevented the 'excitatory' cardiovascular effect of i.v. GABA in reserpine pretreated, guinea-pigs anaesthetized with barbitone. 8 In adrenalectomized guinea-pigs or in preparations receiving i.v. phentolamine plus propranolol, GABA produced only a small 'depressant' effect on cardiovascular parameters. 9 These findings demonstrate that GABA exerts a neuromodulatory effect on cardiovascular function via peripheral actions which is influenced by: (a) type of anaesthesia (b) resting values of cardiovascular parameters (c) degree of activity of the sympathetic nervous system and (d) catecholamine release from the adrenal medulla.

Blood-pressure-lowering effect of a novel fermented milk containing γ-aminobutyric acid (GABA) in mild hypertensives

“…Reports addressing the hypotensive effect of intravenous GABA in animals have increased gradually since the 1980s. Dose-dependent effects were observed in the range of 1 -1000 mg=kg (Billingsley & Suria, 1982), and the degree of the hypotensive effect was positively related to the magnitude of the resting BP (Giuliani et al, 1986).…”

Peripheral GABAA receptor‐mediated effects of sodium valproate on dural plasma protein extravasation to substance P and trigeminal stimulation

“…Because decreased vascular resistance, increased endothelial surface area and increased rCBF augment vascular permeability, it seems possible that valproate and GABAA receptor-mediated effects may be mediated by local meningeal events. Previous work showing hypotensive effects of muscimol (Giuliani et al, 1986) are probably irrelevant to this paper because dosages for that study were twenty times higher and the drug was administered intravenously and not intraperitoneally as here. Furthermore, our own data have established that muscimol and valproate do not alter heart rate or blood pressure when monitored for 30 min after intraperitoneal administration.…”

Role of Gut Microbiota in Early Infant Development

“…For example, on day four of lactation, human milk contained 2 g/100 ml oligosaccharides, which declined 20% and 40% by 30 and 120 days of lactation, respectively. 44 Breast milk is also a source of bacteria and contains up to 10 9 microbes/L in healthy mothers. 45 The most frequently encountered bacterial groups include staphylococci, streptococci, corynebacteria, lactobacilli, micrococci, propioni-bacteria and bifidobacteria.…”

“…The diverse bacterial species within this ecosystem each contain a battery of enzymes capable of performing a myriad of different functions, ranging from transformation of substances present in the gut (to less or more toxic compounds), the production of antimicrobial substances active against pathogenic bacteria and stimulation of the immune system 7,8. Moreover, it has been demonstrated that some commensals within the enteric microbiota are able to produce a range of bioactive fatty acids and metabolites such as conjugated linoleic acid (CLA), short chain fatty acids (SCFA) and gamma-amino butyric acid (GABA) which have shown great potential in the treatment of lifestyle diseases including cancer, obesity and cardiovascular disease 9–13. While species of bacteria are found in the acidic conditions of the stomach, the bacterial density progressively increases distally in the intestine 14.…”

“…7,8 Moreover, it has been demonstrated that some commensals within the enteric microbiota are able to produce a range of bioactive fatty acids and metabolites such as conjugated linoleic acid (CLA), short chain fatty acids (SCFA) and gamma-amino butyric acid (GABA) which have shown great potential in the treatment of lifestyle diseases including cancer, obesity and cardiovascular disease. [9][10][11][12][13] While species of bacteria are found in the acidic conditions of the stomach, the bacterial density progressively increases distally in the intestine. 14 Anaerobic and aerobic genera of bacteria inhabit the GIT, 14,15 though the majority are strict anaerobes 16 with Bifi dobacterium, Clostridium, Bacteroides, Lactobacillus and Eubacterium being among the most commonly found enteric bacteria.…”