pH and smooth muscle

Abstract

In this paper, the control of vascular smooth muscle intracellular pH (pHi) and the mechanisms of importance for the vasodilation to acidosis are reviewed. The three transport pathways of importance for the control of pHi are a sodium-coupled bicarbonate transport, a Na,H-exchanger and a Cl,HCO3- exchange. While the two latter pathways are present in all smooth muscle cells studied, the sodium-coupled bicarbonate transport may be present in two forms which are either coupled to chloride efflux or are independent of chloride. The chloride-independent pathway seems electroneutral, indicating a 1:1 stoichiometry. All three transporters can be activated by vasoactive hormones and the second messengers involved are under intense investigation. With respect to the mechanisms involved in the vasodilation to acidosis, there seems to be a nitric oxide-dependent pathway as well as a direct effect of acidosis on the smooth muscle cells. In some preparations, prostanoids may also be involved. The direct vasodilator effect of acidosis is probably mediated through reduction of extracellular pH and the acidosis is associated with a reduction of the intracellular calcium concentration, which could explain the reduction of smooth muscle tone.

Effects of acid-base imbalance on vascular reactivity

“…The consensus is that this transporter accounts for a significant role in the control of pH i , except for the guinea pig femoral artery where it has a very small fraction of acid extrusion. Additionally, there is a very consistent finding that smooth muscles have an Na + -independent Cl -/HCO 3 -exchange pathway that has been shown in cultured and intact vascular preparations (14)(15)(16).…”

“…Thus, reduction of extracellular pH is probably more important for vasodilation than the associated reduction in pH i . It is becoming clear that the reduction of [Ca 2+ ] i is involved significantly, although the role of membrane potential is not yet understood (14).…”

Smooth Muscle

“…Both acute and steady-state reduction of pHi (with maintained extracellular pH, pHo) is associated with force development, which may be due to proton-induced release of intracellular calcium. The reduction of tone seen with reduction of pHo is therefore unlikely to be due to the concomitant reduction in pHi (Aalkjrer & Peng, 1997). The mechanism for the reduction of tone with a reduction of pHo is probably due to a reduction of intracellular calcium, although a reduction of calcium sensitivity of the contractile machinery may also play a role.…”

“…In vascular smooth muscle Na+ -H+ exchange, as well as Na+-dependent and Na+-independent HC0 3 -transport, have been demonstrated and are involved in the regulation of pHi (Aalkjrer & Peng, 1997). Substantial physiological and molecular information is available with regard to Na + -H+ exchange.…”

Na+/H+ Exchange and Hypoxic Pulmonary Hypertension

“…1), the relative significance of these various transport mechanisms to control of pH i under basal conditions appears to vary by experimental organism, tissue, and cell type. All four of these ion transporters have been described in various types of vascular smooth muscle [1][2][3][4] and, with the exception of Na + -HCO 3 − cotransport, modulate pH i in pulmonary arterial smooth muscle cells (PASMCs). [5][6][7] Of these, NHE plays a significant role in regulating PASMC pH i , under both resting and stimulated conditions.…”