Effects of intracellular alkalinization on resting and agonist-induced vascular tone

Danthuluri, N. Raju; Deth, Richard C.

doi:10.1152/ajpheart.1989.256.3.h867

Cited by 19 publications

(25 citation statements)

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“…On the other hand, NH« + slowly enters into the cell and releases H + , leading to a gradual normalization of pH,. 16 Thus, NH,Cl-induced attenua- tion of acetylcholine relaxation may follow pH, alteration with NH4CI treatment. Moreover, amiloride normalized the suppressive effect of the 10-minute treatment of NH4CI but not the 0-minute treatment, although nigericin inhibited NHiCl-induced attenuation irrespective of the treatment period.…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis is supported by the present finding that the effect of NH4CI disappeared in a time-dependent fashion ( Table 2). When NH4CI was added extracellularly, NH 3 rapidly moves into intracellular spaces and binds H + , resulting in intracellular alkalinization, in vascular smooth muscle 16 and endothelial 17 cells. On the other hand, NH« + slowly enters into the cell and releases H + , leading to a gradual normalization of pH,.…”

Section: Discussionmentioning

confidence: 99%

“…Intracellular alkalinization by NH 4 C1 gradually disappeared, 16 -17 so we examined the effects of different treatment periods of NH,G (0-minute and 10-minute treatments) on acetylcholine relaxation. Norepinephrine precontraction was started immediately after NH 4 CI administration in the 0-minute treatment and 10 minutes after NFL.C1 administration in the 10-minute treatment.…”

Section: Experiments 2: Time-dependent Effect Ofnhjcl Treatment On Acementioning

confidence: 99%

“…Acetylcholine relaxation was also examined after inhibition of NHiCl (0-minute and 10-minute treatments)-induced alkalinization by 10" 6 mol/L nigericin. Moreover, we tested the influence of Na + -H + antiport inhibition with 10" 5 mol/L amiloride 16 on the action of NH,G.…”

Section: Experiments 2: Time-dependent Effect Ofnhjcl Treatment On Acementioning

confidence: 99%

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Inhibitory effect of ammonium chloride on acetylcholine-induced relaxation.

Ando

Fujita

1994

Hypertension

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We designed the present study to clarify whether the intracellular pH change by ammonium chloride influences endothelium-dependent relaxation in thoracic aorta of 9-week-old Sprague-Dawley rats. Intracellular alkalinization with 3 mmol/L ammonium chloride, which did not affect resting vascular tone, attenuated acetylcholine-induced relaxation but not nitroglycerin vasodilation. Acetylcholine relaxation was more inhibited by a shorter duration of treatment. Thus, change in intracellular pH may be important in the effect because the alkalinizing effect of ammonium chloride disappears gradually. In support of this, the proton ionophore nigericin abolished the effect. Also, amiloride shortened the effect of ammonium chloride, suggesting that intracellular pH plays a role: sodium-proton antiport antagonizes the disappearance of ammonium chloride-induced intracellular alkalinization. The synthesis of vasoconstrictor prostaglandins, such as thromboxane A 2 , may be stimulated during acetylcholine A bnormal sodium-proton (Na + -H + ) antiport and /\ intracellular pH (pH,) have been reported in A. ^ hypertensive 1 and diabetic 14 subjects. It has been reported that increased pH, enhances and decreased pHi suppresses vascular tone, reactivity, or both. 58 Thus, a change in pH, might be important in the abnormal regulation of vascular tone in both diseases. The pH; of vascular smooth muscle cells may be important because change in the pH, of smooth muscle cells has been demonstrated to play a role in the regulation of vascular tone. 67 On the other hand, abnormal endothelial function may also result from increased pH, of endothelium because a few investigators have reported that endothelial pH, may affect vascular tone.5 -8 High CO 2 tension, which causes acidemia, attenuated norepinephrine contraction, which was partially normalized by denudation of the inner surface of the aorta. 5 Moreover, in a recent study, 8 we altered acetylcholine-induced relaxation by modifying Na + -H + antiport with low Na + medium and amiloride. However, it has not yet been concluded whether pHj change in endothelial cells contributes to the regulation of vascular tone.Vasoconstrictor prostaglandins have been suggested to contribute to vasoconstriction induced by intracellular alkalinization. Vasoconstriction with alkalosis was accompanied by increased levels of thromboxane B 2 and 6-ketoprostaglandin F la in perfused rabbit lungs. © 1994 American Heart Association, Inc.treatment, resulting in the attenuation of acetylcholine relaxation, because the relaxation was abolished by treatment with the phospholipase A 2 inhibitor quinacrine, cyclooxygenase inhibitor indomethacin, prostaglandin H 2 /thromboxane A 2 receptor antagonist S1452, and thromboxane A 2 synthase inhibitor dazmegrel. Phospholipase A 2 may contribute to the effect of intracellular alkalinization, which is compatible with the fact that the optimal pH of phospholipase A 2 is neutral to alkaline. In addition, superoxide dismutase attenuated the effect of ammonium chloride....

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Experiments 2: Time-dependent Effect Ofnhjcl Treatment On Acementioning

confidence: 99%

Section: Experiments 2: Time-dependent Effect Ofnhjcl Treatment On Acementioning

confidence: 99%

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Inhibitory effect of ammonium chloride on acetylcholine-induced relaxation.

Ando

Fujita

1994

Hypertension

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“…Nevertheless, two lines of evidence indicate that these two inhibitors block IRCM-induced vasodilatation via different mechanisms: (i) iodixanol-induced relaxation was unaffected by the presence of EIPA and (ii) combined incubation with both inhibitors synergistically attenuated iohexol-induced relaxation, whereas the effects of ouabain against iodixanol-induced vasodilatation were not enhanced by EIPA. Stimulation of Na' -H' exchange elevates intracellular pH ([pH]i), which mediates relaxation of rat aorta precontracted with PhE or K+ (Danthuluri & Deth, 1989) and in cardiac myocytes causes a fall in intracellular Ca2" concentration ([Ca2+]J) by 60% (Kim et al, 1987). Levitsky and Benevolensky (1986) showed that elevated [pH]i enhanced Ca2" sequestration by cardiac sarcoplasmic reticulum.…”

Section: Discussionmentioning

confidence: 99%

Ionic mechanisms contributing to the vasorelaxant properties of iodinated contrast media: a comparison of iohexol and iodixanol in the rabbit isolated aorta

Pitman¹,

Karlsson²,

Griffith³

1996

British J Pharmacology

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1 We have used rings of rabbit thoracic aorta to investigate the vasorelaxant properties of two different classes of non-ionic iodinated radiographic contrast media (IRCM) and the mechanisms, underlying their mode of action. lohexol (a triiodinated monomer) was compared with iodixanol (a hexaiodinated dimer).2 lohexol and iodixanol both relaxed phenylephrine (0.3 gM) constricted rabbit aorta in a concentration-dependent manner that did not depend on the presence of an intact endothelium. When expressed as a function of iodine concentration, iodixanol caused significantly less relaxation than iohexol. However, the extent of relaxation was similar for both IRCM when expressed on a molar basis. Furthermore, increasing the molarity of the buffer to comparable levels with mannitol evoked only a small (-15%) relaxation of phenylephrine-induced tone.3 Ouabain (10 gM) significantly inhibited both iohexol-and iodixanol-induced relaxations by -30%.5-(N-Ethyl-N-isopropyl)-amiloride (EIPA, 100 nM) significantly inhibited iohexol-induced relaxation to the same extent as ouabain, but did not alter the vasorelaxant effect of iodixanol. Co-incubation with ouabain and EIPA had an additive effect in the case of iohexol, increasing inhibition of relaxation to -60%, whereas inhibition of iodixanol-induced relaxation by the combination of ouabain plus EIPA did not differ from that of ouabain alone. 4 Replacing NaCl with N-methyl-D-glucamine (NMDG) to lower extracellular [Na+] and thereby inhibit Na+ -Ca2" exchange, attenuated the relaxation evoked by iohexol or by iodixanol (by -25%) in each case. 5 We conclude that iohexol-and iodixanol-induced vasorelaxation in rabbit aorta is mediated through a direct action on vascular smooth muscle that is not simply a consequence of altered osmolality. It involves modulation of the Na+-K+ ATPase and, in the case of iohexol, Na+-H+ exchange. Both agents also appear to modulate Na+ -Ca2+ exchange, through direct and/or indirect mechanisms. This is the first study to show specific pharmacological differences between monomeric and dimeric contrast media in vascular smooth muscle.

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Cellular Actions of Endothelin in Vascular Smooth Muscle

Brock¹,

Danthuluri²

1992

Endothelin

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Effects of intracellular alkalinization on resting and agonist-induced vascular tone

Cited by 19 publications

References 0 publications

Inhibitory effect of ammonium chloride on acetylcholine-induced relaxation.

Inhibitory effect of ammonium chloride on acetylcholine-induced relaxation.

Ionic mechanisms contributing to the vasorelaxant properties of iodinated contrast media: a comparison of iohexol and iodixanol in the rabbit isolated aorta

Cellular Actions of Endothelin in Vascular Smooth Muscle

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