Stroke-prone SHR vascular muscle Ca2+ current amplitudes correlate with lethal increases in blood pressure.
Studies on the possible causal relationship between the Ca2+ channel current density in the vascular muscle cell (VMC) and increases in blood pressure were extended by a comparison of stroke-prone spontaneously hypertensive rats (SP-SHR) with N/nih outbred normotensive rats. Maximal amplitudes of both L-type and T-type Ca2+ channel currents were significantly increased in SP-SHR without a difference in cell capacitance. SP-SHR peak current amplitudes in 20 mM Ba2+ averaged 446 +/- 64 pA while N/nih averaged 156 +/- 25 pA (clearly separated statistically). Both L-type and T-type Ba2+ currents (IBa) were significantly increased in SP-SHR, shown also by peak current frequency distributions. There was a significant shift to the left of both activation (7 mV) and inactivation (15 mV) current-voltage (I-V) plots. SP-SHR IBa recovery from inactivation was significantly slower (103 versus 61 ms) than in N/nih VMC. The increases in SP-SHR IBa amplitude under maximized conditions correlated with increases in blood pressure. Together with earlier observations of increased vascular muscle Ca2+ current density coexistent with blood pressure elevation in Kyoto-Wistar SHR, these data provide evidence for altered function of Ca2+ channels as a fundamental component of hypertension. Since the Ca2+ channel alterations exist in venous VMCs of newborn SP-SHR rats (in a low pressure blood vessel and at a time when increased Ca2+ current density could not be an effect of increased blood pressure), our results add to the growing evidence of Ca2+ channel abnormalities as a cause of genetic hypertension.
Self
D A
DA
Oregon Regional Primate Research Center Oregon Health Sciences University, Beaverton 97006.
Bian
K
K
Mishra
S K
SK
Hermsmeyer
K
K
D000818:Animals; D001401:Azygos Vein / Q000378:metabolism* / Q000473:pathology; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D002561:Cerebrovascular Disorders / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR
D015220:Calcium Channels; D002118:Calcium