pH and Vascular Tone

Ighoroje, Ahbor Dolly Awani (1987) pH and Vascular Tone. PhD thesis, University of Glasgow.

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The mechanisms by which extracellular pH (pH0) and intracellular pH (pHi) affect vascular tone, and by which pHi itself is regulated in the vascular smooth muscle cells, have been investigated. The majority of experiments were carried out with isolated rabbit ears activated with 10 -6M noradrenaline and perfused at constant flow. Other preparations studied were perfused whole femoral beds of rabbits and frog whole body. The perfusing solutions were phosphate, Hepes or CO2 / HCO3- buffered Ringer's having Cl- as the bulk anion, and appropiately oxygenated. pHi was modified at constant pH0 using two different procedures, one was the application and withdrawal of CO2 and the other was the "NH4+ pulse" technique, which involved the application and washout of NH4+. The procedures which can be expected to lower pHi at constant pH0 both raised tone while the reverse steps reduced it. With every fluid used NH4+ application or lowering / withdrawal of CO2 dilated the vascular bed while NH4+ withdrawal or elevation / application of CO2 constricted it. The time courses of the changes in tone were reminiscent of pH responses to the above procedures, shown by intracellular pH electrode measurement in various cell types e. g. vas deferens (Aicken, 1984), squid giant axon (Thomas, 1974, '84) and pHi estimations by N. M. R. techniques with mixed arterial preparations (Dawson, Spurway and Wray, 1985) - in all these cases extracellular NH4+ transiently raises cytoplasmic pH while the subsequent washout carries it for a period below the control level. By contrast with the mammalian preparations NH4+ application actually vasoconstricted while its withdrawal vasodilated. The phenomena were investigated under varying ionic and external conditions and were compared under three pH0's: 6.7, 7.2, 7.7. There were no qualitative differences under all conditions though quantitatively there were variations. The results excluded all the explanations of the classical pH0 effect invoking direct H+ inhibition of intracellular events. Therefore displacement of Ca2+ by H+ from sequestering sites (S. R; mitochondria) other than the myofibrils themselves was proposed to account for these pHi effects observed. Some interventions, known to affect pHi homeostasis in other cells, were employed to establish possible mechanisms of pHi regulation. Replacement of all Cl- with PhSO3-, or H2PO4- with HCO3, and the application of S.I.T.S. or amiloride all retarded the adaptation of tone from NH4+ dilatation. Replacement of all NaO+ with Li+, choline, sucrose or K+, replacement of H2 PO4 with HCO3- and applications of S.I.T.S. , ouabain, amiloride and its derivatives all retarded to varying degrees the adaptation of tone from the washout constriction. Notably among the latter was the 10x greater potency of a claimed Na+ - H+ exchange inhibitor than of a claimed 2Na+ -Ca2+ inhibitor. Quantitative considerations such as this lead to the conclusion that Cl- -HCO3- exchange plays the major role in the elimination of alkaline load while excess H+i are eliminated mainly by a Na+-H+ exchange. Adaptation of tone from both dilatation and constriction is probably also influenced by changes of membrane potential and by the movements of other ions (Cl-, Ca2+, K+ and NH4+) which must occur in parallel with the changing rates of antiportation. It was incidentally noted that, while amiloride is vasodilatory, its derivatives may have either vasodilatory or vasoconstrictory effects on NA-activated vessels. The significance of the work for normal physiology is considered to be: (a) its refutation of proposals that dilatory effects of extracellular acidity are mediated by intracellular acidification. (b) its indication that changes of body fluid pH brought about by PCO2 variation are likely to produce tone responses smaller than -or even, at times, opposite to - the responses produced when pH0 is changed in identical amounts by variation of [HCO3-]0.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Physiology
Date of Award: 1987
Depositing User: Enlighten Team
Unique ID: glathesis:1987-77493
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53

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