Norepinephrine-induced calcium signaling pathways in afferent arterioles of genetically hypertensive rats.
This study provides new information about the relative importance of calcium mobilization and entry in the renal vascular response to adrenoceptor activation in afferent arterioles isolated from 7- to 8-wk-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Intracellular free calcium concentration ([Ca(2+)](i)) was measured in microdissected arterioles utilizing ratiometric photometry of fura 2 fluorescence. There was no significant strain difference in baseline [Ca(2+)](i). Norepinephrine (NE; 10(-6) and 10(-7) M) elicited immediate, sustained increases in [Ca(2+)](i). The general temporal pattern of response to 10(-6) M NE consisted of an initial peak and a maintained plateau phase. The response to NE was partially blocked by nifedipine (10(-6) M) or 8-(N,N-diethylamino) octyl-3,4,5-trimetoxybenzoate (TMB-8; 10(-5) M). A calcium-free external solution abolished the sustained [Ca(2+)](i) plateau response to NE, with less influence on the peak response. In the absence of calcium entry, TMB-8 (10(-5) M) completely blocked the calcium response to NE in WKY but not SHR, suggesting strain differences in mobilization. A higher concentration of TMB-8 (10(-4) M), however, blocked all discernible mobilization in both strains. We conclude that there are differences in Ca(2+) handling in renal resistance vessels between young WKY and SHR with respect to mobilization stimulated by alpha-adrenoceptors. Afferent arterioles of young SHR appear to have a larger inositol-1,4,5-trisphosphate-sensitive pool or release from a site less accessible to TMB-8.
Salomonsson
M
M
Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545, USA.
Arendshorst
W J
WJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000033:anatomy & histology / Q000098:blood supply*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002614:Chelating Agents; D014662:Vasoconstrictor Agents; D004533:Egtazic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine