Vascular muscle calcium channel modulation in hypertension

Indications of membrane alterations in vascular muscle cells of spontaneously hypertensive rats (SHR), compared to their Kyoto-Wistar normotensive controls (WKY), have led to further investigation of calcium channels. Previous work from this laboratory had shown the increased probability for opening of the longer-lasting (L-type) calcium channels in SHR, suggesting differences in number or modulation. These experiments have been carried out on the azygos vein of neonatal rats because that preparation has been characterized electro-physiologically, pharmacologically, and by contractile parameters. Divalent (inward) ion currents through the L-type calcium channels are more readily carried by barium than by calcium, a characteristic that is not true for the transient (T) channels. Because there is an increased ratio of L to T calcium channels in SHR, the substitution of barium for calcium is more apparent for inward current amplitude in SHR than in WKY. This increase in the sustained L-type calcium currents, appearing without increased blood pressure on the venous side in newborn animals, is suggestive of a genetic membrane alteration that could contribute to vascular muscle membrane changes important in the development of increased blood pressure. Description and differentiation of the ribbon shaped vascular muscle cells from cardiac muscle cells, and the potential for confusion of the two in older animals, was addressed. The predominance of T-type calcium currents in these azygos vein cells, which is likely to correlate with the predominance of rapid spontaneous contractions, offers a compelling reason for selection of azygos veins in Ca2+ channel comparisons to establish etiologic factors at the cell level in hypertension.