Enhanced response to AVP in the interlobular artery from the spontaneously hypertensive rat.
Arginine vasopressin (AVP) induces exaggerated intracellular free calcium (Cai2+) responses in preglomerular smooth muscle cells from young spontaneously hypertensive rats (SHR) due to increased density of the AVP V1a receptor. The intention of the present paper was to examine the relative contribution of afferent arterioles (AA) and interlobular artery (ILA) in AVP- and norepinephrine-induced calcium signaling. The kidneys were perfused with agar solution in vivo, and thin cortical slices were enzyme digested to produce isolated agar-filled vascular fragments. Calcium responses were recorded in fura 2-loaded cells by Ca2+ imaging. Diameter changes were measured after AVP stimulation and mRNA for V1a was measured on isolated vessel fragments. SHR had a significantly higher baseline calcium ratio and lower resting diameter compared with normotensive Wistar-Kyoto rats (WKY). Stimulation with AVP (10(-7) M) in ILA fragments from SHR induced a ratio increase of 0.49 +/- 0.09, significantly higher than the ratio increase in AA from SHR (0.20 +/- 0.03, P < 0.01) and in ILA from WKY (0.24 +/- 0.03, P < 0.01). Stimulation with norepinephrine (10(-7) M) induced responses homogeneously distributed between the segments and strains. Nifedipine treatment or removal of external calcium (Cao2+) reduced the norepinephrine-induced peak response. Both norepinephrine- and AVP-induced sustained responses were abolished after Cao2+ removal in SHR and WKY (P < 0.01). Measurements of V1a receptor mRNA on isolated segments showed a threefold increase in ILA from SHR. The present findings indicate that the exaggerated Ca2+ and contractile response to AVP in SHR is mainly mediated through ILA vasoconstriction.
Hansen
Frank H
FH
Renal Research Group, Institute of Medicine, University of Bergen, Bergen, Norway. Frank.Hansen@med.uib.no
Vågnes
Øyvind B
ØB
Iversen
Bjarne M
BM
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000503:physiopathology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012076:Renal Agents / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D012076:Renal Agents; D001127:Arginine Vasopressin; D009543:Nifedipine