Paracetamol metabolism by endothelial cells - Potential mechanism underlying intravenous paracetamol-induced hypotension.

It was shown previously that a metabolite of acetaminophen (APAP), N-acetyl-p-benzoquinone imine (NAPQI), is a potent vasodilator, which could underlie the hypotension observed when APAP is administered intravenously. However, it is unknown whether APAP metabolism to NAPQI is possible in the vasculature. In this study, we examine the hypothesis that APAP is metabolized by cytochrome P450 enzymes within the endothelium, which may be accelerated in critically ill patients by the presence of elevated myeloperoxidase (MPO).

Vascular smooth muscle BK channels limit ouabain-induced vasocontraction: Dual role of the Na/K-ATPase as a hub for Src-kinase and the Na/Ca-exchanger.

Large-conductance, calcium-activated potassium channels (BK channels) and the Na/K-ATPase are expressed universally in vascular smooth muscle. The Na/K-ATPase may act via changes in the intracellular Ca concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels.

Polymodal K channel modulation contributes to dual analgesic and anti-inflammatory actions of traditional botanical medicines.

Pain and inflammation contribute immeasurably to reduced quality of life, yet modern analgesic and anti-inflammatory therapeutics can cause dependence and side effects. Here, we screened 1444 plant extracts, prepared primarily from native species in California and the United States Virgin Islands, against two voltage-gated K channels - T-cell expressed Kv1.3 and nociceptive-neuron expressed Kv7.

Crucial role for sensory nerves and Na/H exchanger inhibition in dapagliflozin- and empagliflozin-induced arterial relaxation.

Aims: Sodium/glucose transporter 2 (SGLT2 or SLC5A2) inhibitors lower blood glucose and are also approved treatments for heart failure independent of raised glucose. Various studies have showed that SGLT2 inhibitors relax arteries, but the underlying mechanisms are poorly understood and responses variable across arterial beds. We speculated that SGLT2 inhibitor-mediated arterial relaxation is dependent upon calcitonin gene-related peptide (CGRP) released from sensory nerves independent of glucose transport.