Open AccessImpaired control of L-type voltage-dependent calcium channels in experimental hypertension
Author(s) -
M Pintérová,
Silvia Líšková,
Z Dobešová,
Michal Behuliak,
Jaroslav Kuneš,
Josef Zicha
Publication year - 2009
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931914
Subject(s) - nifedipine , nitric oxide , endocrinology , vasodilation , medicine , voltage dependent calcium channel , chemistry , vasoconstriction , calcium , sympathetic nervous system , norepinephrine , l type calcium channel , blood pressure , dopamine
Blood pressure (BP) level results from the balance ofvasoconstrictors (mainly sympathetic nervous system) andvasodilators (predominantly nitric oxide and endothelium-derivedhyperpolarizing factor). Most of the forms of experimentalhypertension are associated with sympathetic hyperactivity andendothelial dysfunction. It is evident that nitric oxide andnorepinephrine are antagonists in the control of calcium influxthrough L-type voltage-dependent calcium channels (L-VDCC).Their effects on L-VDCC are mediated by cGMP and cAMP,respectively. Nevertheless, it remains to determine whether thesecyclic nucleotides have direct effects on L-VDCC or they actthrough a modulation of calcium-activated K+ and Cl- channels which influence membrane potential. Rats with genetic or salthypertension are characterized by a relative (but not absolute)NO deficiency compared to the absolute enhancement ofsympathetic vasoconstriction. This dysbalance of vasoconstrictorand vasodilator systems in hypertensive animals is reflected bygreater calcium influx through L-VDCC susceptible to theinhibition by nifedipine. However, when the modulatory influenceof cyclic nucleotides is largely attenuated by simultaneousganglionic blockade and NO synthase inhibition, BP ofspontaneously hypertensive rats remains still elevated comparedto normotensive rats due to augmented nifedipine-sensitive BPcomponent. It remains to determine why calcium influx throughL-VDCC of hypertensive rats is augmented even in the absence ofmodulatory influence of major vasoactive systems (sympatheticnervous system, nitric oxide).