Cholinesterase activity in human pulmonary arteries and veins

Abstract

1 Human isolated pulmonary vessels were treated with cholinesterase (ChE) inhibitors to determine the role of these enzymes in regulating vascular muscle tone. In addition, kinetic parameters were determined for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in human pulmonary vessel homogenates. 2 Carbachol (CCh) and acetylcholine (ACh) were equipotent contractile agonists in human pulmonary arteries (pD 2 values, 5.28+0.05 and 5.65+0.16; E max , 0.91+0.26 and 0.98+0.30 g wt. for CCh and ACh, respectively; n=7). In venous preparations, ACh was ineective and CCh induced small contractions (E max , 0.08+0.04 g wt.; n=13). 3 In human pulmonary arteries following pretreatment with tetraisopropylpyrophosphoramide (iso-OMPA, 100 mM), an increased sensitivity to the contractile agonist ACh was observed (pD 2 values, 5.80+0.13 and 6.37+0.19 for control and treated preparations, respectively; n=5). This pretreatment had no eect on the CCh concentration response curve. In contrast, human pulmonary veins pretreated with iso-OMPA failed to elicit a contractile response to ACh. 4 Neither Iso-OMPA nor neostigmine elicited concentration-dependent contractions in human isolated pulmonary arteries or veins. These results suggest the absence of sucient spontaneous release of ACh to modulate human pulmonary vessel basal tone. 5 CCh was less potent than ACh in relaxing precontracted human isolated pulmonary arteries (pD 2 value, CCh: 6.55+0.15 and ACh: 7.16+0.13, n=4) and veins (pD 2 value, CCh: 4.95+0.13; n=5 and ACh: 5.56+0.17; n=6). Pretreatment of vessels with either iso-OMPA or neostigmine did not modify ACh relaxant responses in either type of preparation. 6 In human pulmonary veins, the ChE activity was two fold greater than in arteries (n=6). V max for AChE was 1.73+0.24 and 3.36+0.26 miu mg 71 protein in arteries and veins, respectively, whereas V ss for BChE was 1.83+0.22 and 4.71+0.17 miu mg 71 protein, in these respectively. 7 In human pulmonary arteries, BChE activity may play a role in the smooth muscle contraction but not on the smooth muscle endothelium-dependent relaxation induced by ACh. A role for ChE activity in the control of venous tone is presently dicult to observe, even though this tissue contains a greater amount of enzyme than the artery.

Prostacyclin release and receptor activation: differential control of human pulmonary venous and arterial tone

“…A variety of events could explain this differential sensitivity to ACh, such as, the enzymatic degradation of ACh, the enzymatic synthesis of endothelial mediators NO and/or PGI 2 and the consecutive activation of prostanoid receptors on the underlying smooth muscle. The differential sensitivity to ACh between human pulmonary arteries and veins was not associated with alterations in cholinesterase activity since cholinesterase selective inhibitors do not modify ACh relaxations (Walch et al, 1997). The difference in ACh relaxant effects in artery and vein was also not due to a difference of NO sensitivity.…”

“…The effect of L-NOARG in the arterial preparations only unmasked the contractile activity of ACh (Norel et al, 1996). In the veins since there is no contraction induced by ACh (Walch et al, 1997), the reduced ACh relaxation observed in the presence of L-NOARG was entirely associated with the reduced production of NO. L-NOARG has also been reported to completely abolish the bradykinininduced relaxation in porcine pulmonary veins, but only partially in arteries (Fe´le´tou et al, 1995) data that further support a preferential NO regulation in pulmonary veins when compared with pulmonary arteries.…”

“…In several species, the relaxant effect of ACh in pulmonary arteries and veins has been reported to be different, since veins are insensitive to this relaxant agonist (De Mey & Vanhoutte, 1982;Gruetter & Lemke, 1986;Ignarro et al, 1987;Kemp et al, 1997;Shi et al, 1997). In contrast, ACh has been reported to relax human pulmonary arteries and veins with the latter tissue being less sensitive (Walch et al, 1997). Studies in a variety of human systemic arteries and veins derived from either the same organ or tissue have reported similar results, that is, ACh has no or only a weak relaxant action in veins when compared with arteries (mammary vessels, Lu¨scher et al, 1988; vascular bed of the forearm, Kemme et al, 1995;hand vessels, Arner & Ho¨gesta¨tt, 1991;and epicardial coronary vessels, Saetrum Opgaard & Edvinsson, 1996).…”

Expression of the High-affinity Choline Transporter CHT1 in Rat and Human Arteries

“…Arterial and microvascular endothelial cells release acetylcholine (ACh) (Milner et al 1989;Kawashima et al 1990;Ikeda et al 1994) and have been shown to express both the ACh-synthesizing enzyme, choline acetyltransferase (ChAT) (Parnavelas et al 1985;Haberberger et al 2000;Kirkpatrick et al 2001) and the vesicular acetylcholine transporter (VAChT) (Haberberger et al 2000;Kirkpatrick et al 2001) that shuffles ACh from its cytoplasmatic site of synthesis into storage vesicles in the cholinergic nerve terminal. Extracellular ACh is rapidly deactivated by hydrolysis into acetate and choline by cholinesterases, which are also abundantly present in the arterial wall (Szczech and Godlewski 1988;Altiere et al 1994;Walch et al 1997). A high-affinity re-uptake of choline is essential for a new cycle of cellular ACh synthesis, and in cholinergic neurons this re-uptake is the rate-limiting step in cholinergic signaling (Haga and Noda 1973;Kuhar and Murrin 1978).…”

Relationship between serum cholinesterase level and urinary bladder activity in patients with or without overactive bladder and/or neurogenic bladder

“…It has been reported that AChE inhibitor decreased the residual urine volume by restoring voiding function in rats with BOO (12), suggesting that AChE may have an important role in modulating acetylcholine-induced bladder contraction. In airway smooth muscles and pulmonary blood vessels, not only AChE but also BuChE play an important role in controlling acetylcholine-induced responses (2,21). It has also been reported that coapplication of both enzymes resulted in a 1330% prolongation in the decay of electric field stimulation-induced contractions, indicating that both enzymes are involved in the regulation of acetylcholine (3).…”