Functional pharmacological characterization of SER100 in cardiovascular health and disease
Mesenteric arteries
Cardiovascular physiology
DOI:
10.1111/bph.13634
Publication Date:
2016-09-26T01:36:56Z
AUTHORS (7)
ABSTRACT
Background and Purpose SER100 is a selective nociceptin (NOP) receptor agonist with sodium‐potassium‐sparing aquaretic anti‐natriuretic activity. This study was designed to characterize the functional cardiovascular pharmacology of in vitro vivo , including experimental models disease. Experimental Approach Haemodynamic, ECG parameters heart rate variability (HRV) were determined using radiotelemetry healthy, conscious mice. The haemodynamic vascular effects also evaluated two disease, spontaneously hypertensive rats (SHR) murine hypoxia‐induced pulmonary hypertension (PH). To elucidate mechanisms underlying SER100, acute blood pressure recordings performed anaesthetized mice, reactivity rodent aorta mesenteric arteries response electrical‐ agonist‐stimulation assessed. Key Results caused NOP receptor‐dependent reductions mean arterial that independent NO. hypotensive vasorelaxant actions potentiated SHR compared Wistar Kyoto. Moreover, reduced several indices disease severity PH. Analysis HRV indicated decreased low/high frequency ratio, an indicator sympatho‐vagal balance, electrically stimulated mouse inhibited sympathetic‐induced contractions. Conclusions Implications exerts chronic bradycardic rodents, systemic hypertension. produces its effects, at least part, by inhibition cardiac sympathetic may represent novel therapeutic candidate
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