Abstract 3142: Exaggerated KCa Channel Current Activity Accounts for Reduced Myogenic Constriction in the Cerebral Vasculature of the Fawn Hooded Hypertensive (FHH) rats
The ionic mechanism by which pressure induces myogenic arterial constriction is not completely understood. In the present study we compared the Fawn Hooded Hypertensive (FHH) rat strain bred that does not autoregulate CBF and the FHH.1BN rat strain created by transfer of a 2.6 Mb region of a Brown Norway (BN) rat chromosome 1 and introgressed into the FHH genetic background and recovered the myogenic phenotype, with respect to KCa channel activity and pressure-induced myogenic constriction. We investigated the functional role of Ca2+-activated K+ channel in the impaired pressure-induced myogenic response in cannulated and pressurized middle cerebral arterial segments of FHH and compared with that of the FHH.1BN rat strain. The cannulated arterial segments of FHH rat strain elicited significantly reduced pressure-induced myogenic constriction, whereas those of the FHH.1BN exhibited more than 40-50 % constriction or reduction in diameter during step increases in intravascular pressure from 40 to 140 mmHg. Pretreatment of the he FHH rat cerebral arterial segments with the KCa channel inhibitor iberiotoxin (100 nM) rendered the FHH rat cannulated arterial segments elicit near equal level of myogenic constriction as that of the FHH.1BN. The magnitude and density (pA/pF) of a macroscopic whole-cell KCa channel current recorded from FHH and FHH.1BN rat cerebral arterial muscle cells during a 10 mV step depolarization from -70 mV to +80 mV was 2- to 3-fold greater in the FHH than that in the FHH.1BN rat cerebral arterial muscle cells. Similarly, the NPo of the KCa single-channel currents recorded at +40 mV using symmetrical KCl solution was significantly higher in the FHH (0.0035 ± 0.0002) than in the FHH.1BN (0.0013 ± 0.0003, n =5), albeit the unitary conductances were not different. These findings indicate that exaggerated KCa channel current activity in the FHH rat cerebral arterial muscle cell membrane could account for the impaired pressure-induced myogenic constriction in the FHH rat strain and may have implications for stroke susceptibility in the FHH rat model.
- © 2012 by American Heart Association, Inc.