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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the hemodynamic and electrophysiological effects of UR-8225, a new potassium channel opener with those of levcromakalim. UR-8225 and levcromakalim (0.03-1 mg/kg) dose-dependently decreased mean arterial pressure (MAP) in conscious spontaneously hypertensive rats (SHR) and deoxycorticosterone-salt (DOCA) hypertensive rats and in conscious and anesthetized normotensive rats. The decrease in MAP was accompanied by a dose-dependent increase in heart rate (HR). Levcromakalim was about twice as potent as an antihypertensive agent, and its hypotensive and tachycardic effects were of longer duration than those of UR-8225. In conscious normotensive rats, the hypotensive response to UR-8225 (1 mg/kg) did not diminish with repeated dosing for 16 days. In conscious SHR, propranolol antagonized the tachycardic response of UR-8225 without affecting its hypotensive response. In anesthetized rats, glibenclamide (3, 10, and 20 mg/kg) dose-dependently reduced the hypotensive effect of the drug. In anesthetized dogs, UR-8225 and levcromakalim (0.01-30 micrograms/kg) dose-dependently decreased MAP and total peripheral resistance (TPR): UR-8225 was approximately 10 times less potent than potent than levcromakalim. UR-8225 had no effect on HR, left ventricular end-diastolic pressure (LVEDP), stroke volume (SV), or cardiac output (CO) but decreased rate-pressure product (RPP) and cardiac work (CW). In contrast, levcromakalim decreased HR, RPP, and CW and increased SV and LVEDP, whereas CO remained unaltered. UR-8225 and levcromakalim (0.1-10 microM) had no effect on the ventricular action potentials (APs), whereas at higher concentrations they shortened the AP duration (APD), an effect that was antagonized by glibenclamide. UR-8225 and levcromakalim decreased the Vmax and shortened the APD of the slow ventricular APs elicited by isoprenaline in K(+)-depolarized ventricular muscle fibers. These results indicated that UR-8225 decreases blood pressure (BP) by reducing TPR. Its electrophysiological and hemodynamic effects were blocked by glibenclamide, which suggests that they may be mediated largely through the activation of ATP-sensitive K+ channels.
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PMID:Cardiovascular effects of the novel potassium channel opener UR-8225. 747 55

Clinical experience and experimental studies have shown that hyperthermia can cause cerebral ischaemia and brain damage. By in vitro experiments with heating, we previously were able to induce carotid artery constriction. The objective of the present study was to clarify the mechanism of this thermal response. Isometric tension was recorded in rabbit carotid artery specimens using organ baths during stepwise temperature elevation. The heating responses were investigated at basal tone, in precontracted vessels, after blocking of adrenergic responses and administration of potassium (K)-channel activators and inhibitors. Stepwise heating of carotid artery strips from 37 degrees C to 47 degrees C induced reproducible graded contraction. The hyperthermic responses were not due to adrenergic stimulation, which were reduced and resistant to neurogenic blockade by tetrodotoxin. Heating-induced contractions were potentiated by the K-channel inhibitors tetraethylammonium, BaCl2, charybdotoxin, and the Na+/K+ ATPase inhibitor ouabain. Levcromakalim (BRL), a K+-channel activator, reduced heating induced contractions. Heating of carotid artery preparations induced reversible graded vasoconstriction proportional to temperature. The heating-induced contractions were not mediated by an adrenergenic process, but rather were due to inhibition of K+ channels, which increases Ca2+ entry. In vivo, this reaction may lead to a disturbance of autoregulation of cerebral blood flow and ischemia with brain damage.
J Stroke Cerebrovasc Dis
PMID:Hyperthermia-induced vasoconstriction of the carotid artery and the role of potassium channels. 1790 11