In Vitro Studies on the Mode of Action of Pinacidil

@article{Weston2012InVS,
  title={In Vitro Studies on the Mode of Action of Pinacidil},
  author={Arthur Henry Weston and Katharine Bray and Susan Duty and Aileen Mcharg and Donald Newgreen and J. S. Southerton},
  journal={Drugs},
  year={2012},
  volume={36},
  pages={10-28}
}
Summary(±) Pinacidil inhibited noradrenaline-induced contractions in rat aorta and portal vein. The spontaneous tone of guinea-pig bronchial and taenia caeci muscles was relaxed and the spontaneous mechanical activity of rat portal vein was abolished. (± ) Pinacidil abolished contractions produced by low concentrations of KCl in rat aorta and portal vein, but had relatively little effect on responses to high KCl concentrations. The mechano-inhibitory effects of (±) pinacidil were antagonised by… 
2 Citations
Long Term Haemodynamic Effects of Pinacidil and Hydralazine in Arterial Hypertension
TLDR
During long term treatment, pinacidil seemed more effective in reducing blood pressure than hydralazine, and cardiac contractility, judged from the systolic time interval ratio PEP: LVET, was lower during treatment withPinacidil compared withHydralazine.
Effects of Long Term Treatment with Pinacidil and Nifedipine on Left Ventricular Anatomy and Function in Patients with Mild to Moderate Systemic Hypertension
TLDR
Pinacidil may be a potentially valuable antihypertensive drug and improve left ventricular diastolic function, measured by the isovolumetric relaxation time, whereas nifedipine did not affect this parameter.

References

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TLDR
It is concluded that pinacidil opens 86Rb-permeable potassium channels in rat aorta and rat portal vein, which is independent of cyclic nucleotide changes and may be responsible for the antihypertensive effect ofPinacidil.
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TLDR
It is concluded that pinacidil and GTN do not share a common relaxant mechanism, and evidence has been obtained thatPinacidil exerts its inhibitory effects by the opening of apamin‐insensitive, 86Rb‐permeable K+ channels.
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TLDR
It is concluded that the inhibitory effects of pinacidil in rat blood vessels are associated with the opening of 86Rb-permeable K+ channels, which produces a low-resistance pathway in the membrane and this inhibits the ability of pressor agents to produce smooth muscle contraction.
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TLDR
In isolated human crural veins studied in vitro pinacidil (0.038-380 microM) caused a concentration-related inhibition of noradrenaline, 18 microM (NA) and 127 mM K+-induced contractions, andPinacidil seems to be more effective in NA- induced contractions than does nifedipine.
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TLDR
The results of these experiments indicate that the vasodilating effect may be caused by a hyperpolarization of the vascular smooth muscle cell membrane.
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  • M. CohenK. Kurz
  • Biology, Medicine
    Journal of cardiovascular pharmacology
  • 1988
TLDR
A review of the literature supports the contention that pinacidil-induced vascular relaxation is a direct effect mediated by a novel mechanism, whereas minoxidil and hydralazine may be converted in vivo to active moieties and/or exert indirect effects more apparent under in vivo than in vitro conditions.
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TLDR
The results suggest that pinacidil is a direct-acting arteriolar dilator, which on a molar base is somewhat more potent than hydralazine, which is predominantly arterial vasodilators.
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TLDR
It may be concluded that pinacidil produces vasodilatation due to interference with the transmembrane influx of Ca2+ into smooth muscle evoked by receptor stimulation but not that due to inhibition in the Ca2- influx associated with K+-induced membrane depolarization.
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TLDR
Pinacidil is a clinically effective novel antihypertensive agent that nonselectively inhibits contractile responses of arterial and other smooth muscle and is a direct‐acting vasodilator.
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