Angiotensin II type 1 receptor modulation of L-type calcium currents in guinea-pig ventricular cells.
OBJECTIVE
To study the cellular mechanism of the effect of Ang II on ICa,L in single guinea-pig ventricular cells by using losartan and 1-(5-lsoquinolinylsulfonyl)-2-Methyl-Piperazine (H-7) as the Ang II type 1 receptor (AT1) inhibitor and protein kinase C inhibitor, respectively.


METHODS
Patch clamp techniques were used to study the cellular mechanism of the effect of Ang II on ICa,L in single guinea-pig ventricular cells.


RESULTS
In the whole cell patch clamp recording model, Ang II stimulated ICa,L in a concentration dependent manner; the maximal effect was obtained at 100 nmol/L (n = 9). At 30 nmol/L, Ang II stimulated peak ICa,L from 11.3 +/- 0.6 pA/pF to 15.3 +/- 0.6 pA/pF (at + 10 mV, n = 9, P < 0.05). 100 nmol/L Losartan, a specific AT1 receptor inhibitor, had no effect on ICa,L (n = 9), but the effect of Ang II on ICa,L was inhibited by 100 nmol/L Losartan. Ang II on ICa,L was also inhibited by 20 mumol/L H-7, a specific protein kinase C inhibitor, whereas H-7 alone has no effect on ICa,L (n = 9).


CONCLUSIONS
Ang II stimulates ICa,L in guinea-pig ventricular cells by binding to AT1 through a transduction pathway involving protein kinase C.
Yang
X
X
Department of Cardiology, First Affiliated Hospital, Suzhou University, Suzhou 215006, China.
Hui
J
J
Jiang
W
W
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology; D016276:Ventricular Function
D057911:Angiotensin Receptor Antagonists; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019808:Losartan