Angiotensin II Responses After Protein Kinase C Activation in Vascular Smooth Muscle Cells of Spontaneously Hypertensive Rats

Publisher Website
Google Scholar
Abstract
To examine the interaction of protein kinase C (PKC) with agonist-induced calcium fluxes in hypertension, cytosolic free calcium ([Ca2+ ]i) was measured in vascular smooth muscle cells (vSMC) of normotensive and spontaneously hypertensive rats (SHR) after incubation with phorbol,-12 myristate,-13 acetate (PMA) and application of angiotensin II (All). To distinguish between calcium influx through voltage-dependent calcium channels and calcium mobilization from intracellular stores, the calcium agonist Bay K 8644 was used. Resting [Ca2+ ]i was 108.0 ± 10.6 nM (mean ± SEM, n = 25) in normotensive and 102.0 ± 11.4 nM(n = 21) in hypertensive cells. After pretreatment with PMA 10-7 M for 60 min, resting [Ca2+ ]i of normotensive vSMC increased to 145.0 ± 13.8 nM (n = 17) while the resting level of the hypertensive cells decreased to 68.0 ± 2.4 nM (n = 14, p < 0.05 as compared with normotensive cells) in hypertensive vSMC. Maximum increase in [Ca2+ ]i induced with 10 M AH for normotensive and hypertensive vSMC was similar: 230.5 ± 34.4 nM (n = 14) and 212.5 ± 26.7 nM (n = 17). After pretreatment with PMA 10~7 M, the maximum increase in [Ca2+ ]i induced by All in hypertensive cells was limited to 108.0 ± 6.2 nM (p < 0.05 as compared with normotensive cells), whereas the increase in [Ca2+ ]i in normotensive vSMC remained the same as before: 211.5 ± 23.4 nM. After administration of 10-5 M Bay K 8644, [Ca2+ ]; increased by 54.3 ± 12.2 nM (n = 4) and 43.4 ± 17.4 nM (n = 5) in normotensive and hypertensive vSMC, respectively. After preincubation with PMA this effect was reduced to 20.3 ± 8.8 nM in normotensive cells and 29.0 ± 4.6 nM in hypertensive cells. We conclude that in hypertensive vSMC either the feedback inhibition of postreceptor signaling after PKC activation is more pronounced or that higher amounts of PKC can be activated.

This publication has 0 references indexed in Scilit: