Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries

Abstract

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Inhibition of neurogenic contractions in renal arteries and of cholinergic contractions in coronary arteries by the presumed inhibitor of ADP-ribosylation factor 6, NAV2729

“…The two vessel types examined here did not show real differences regarding their responses to NAV2729. Rather, they show different characteristics in contractions, as EFS- or noradrenaline-induced contractions do not occur in coronary arteries, while cholinergic contractions typically occur in coronaries but not in interlobar or most other arteries (Li et al 2021 ). Accordingly, we examined EFS-induced contractions only in interlobar arteries, and cholinergic contractions only in coronary arteries.…”

“…Thus, mechanisms underlying unique characteristics of muscarinic contractions, and the molecular basis accounting for inhibition of neurogenic contractions by NAV2729 both remain to be identified. Finally, contractions by angiotensin-II, vasopressin, and purinergic agonists may be systemically or locally relevant in the cardiovascular system, but turned out to be weak (i.e., clearly below 100% of KCl-induced contractions) in our recent study using pig interlobar arteries (Li et al 2021 ), so that these agonists were not examined here.…”

“…As a presentation of all single values in scatter plots was aimed, automatic curve fitting was performed separately for all single experiments, resulting in separate values from each independent experiment. Fitting of sigmoidal concentration response curves by nonlinear regression was performed using the same settings as previously reported (Li et al 2021 ). As recommended in the “GraphPad Curve Fitting Guide” (GraphPad Software, Inc., San Diego, CA, USA), resulting values were checked for plausibility.…”

Inhibition of Human Prostate and Bladder Smooth Muscle Contraction, Vasoconstriction of Porcine Renal and Coronary Arteries, and Growth-Related Functions of Prostate Stromal Cells by Presumed Small Molecule Gαq/11 Inhibitor, YM-254890

“…Regarding renal and coronary arteries, certain differences exist as well: while α 1 -adrenergic contractions are known from most vessel types but do not occur in coronary arteries, cholinergic contractions typically do not occur in renal interlobar arteries ( Moreland and Bohr, 1984 ; Li et al, 2021 ). Accordingly, we examined cholinergic contractions only in coronary arteries.…”

Selective inhibition of neurogenic, but not agonist‐induced contractions by phospholipase A2 inhibitors points to presynaptic phospholipase A2 functions in contractile neurotransmission to human prostate smooth muscle

“…9 Based on findings with picotamide, a dual thromboxane A 2 receptor antagonist and thromboxane synthase inhibitor, inhibiting α 1 -adrenergic besides thromboxane-induced smooth muscle contractions in the human prostate, an involvement of similar mechanisms may be supposed for α 1 -adrenergic smooth muscle contraction in the prostate. 5,9 However, whether PLA 2 activation takes part in α 1 -adrenergic contractions of the prostate as well, is still unknown. Here, we examined effects of different PLA 2 inhibitors on neurogenic and α 1 -adrenergic contractions of human prostate tissues, including the cPLA 2 -selective ASB14780, the cPLA 2 inhibitor AACOCF 3 , and the sPLA 2 -selective YM26734.…”