The present study examined the role of L-/T-type Ca channels and the interaction between these channels and
protein kinase C (PKC) in
hypertension. The isolated perfused hydronephrotic rat kidney model was used to visualize directly the renal microvascular effects of L-/T-type Ca channel blockers (
nifedipine and
mibefradil, respectively).
Nifedipine reversed the
angiotensin II-induced constriction of afferent, but not efferent, arterioles in kidneys from Wistar-Kyoto rats (WKY), and similar magnitude in dilation was observed in spontaneously hypertensive rats (SHR). Although
mibefradil elicited dilation of both arterioles, the afferent arteriolar dilation was less in SHR than in WKY (57+/-5% vs. 80+/-4% reversal at 1 micrommol/L). The pretreatment with
staurosporine did not alter the
angiotensin II-induced afferent arteriolar constriction in WKY, but attenuated this response in SHR. Furthermore,
staurosporine enhanced the
nifedipine-induced afferent arteriolar dilation (62+/-3% vs. 50+/-3% reversal
at 10 nmol/L), and restored the attenuated afferent arteriolar response to
mibefradil in SHR. The pretreatment with
thapsigargin (a blocker of IP3-mediated intracellular
calcium release) prevented the
angiotensin II-induced afferent arteriolar constriction in WKY, but caused a significant constriction of afferent arterioles in SHR and efferent arterioles in WKY and SHR; in this setting,
mibefradil did not alter efferent arteriolar tone. In conclusion, although both L-type (
nifedipine) and T-type Ca channel blockers (
mibefradil) exerted potent vasodilation of rat renal microvessels, these actions were modified by PKC, which determined the afferent arteriolar sensitivity to these blockers in SHR. Furthermore, the enhancement in
nifedipine-induced afferent arteriolar dilation by
staurosporine in SHR suggests that L-type Ca channel activity is augmented in hypertensive animals.