Pharmacological characterization and autoradiographic localization of dihydropyridine-type calcium channels in the kidney of spontaneously hypertensive rats.
1. The pharmacological profile and the microanatomical localization of Ca2+ channels of the L-type were analysed in sections of the kidney of Wistar-Kyoto (WKY) rats and of spontaneously hypertensive rats (SHR) of different ages. 2. [3H]-Nicardipine was used as a ligand. It was bound to sections of rat kidney in a manner consistent with the labelling of Ca2+ channels of the L-type. The density of [3H]-nicardipine binding sites was similar in WKY rats of different ages and in SHR of 2 and 4 months, but was significantly increased in SHR of 6 months. 3. Light microscope autoradiography revealed the highest density of binding sites in the tubular portion of the nephron and to a lesser extent within smooth muscle of renal arteries and renal corpuscles. In SHR of 4 and 6 months the density of [3H]-nicardipine binding sites was increased within the epithelium of proximal tubules and of the loop of Henle and decreased in renal corpuscles in comparison with WKY rats or 2 month old SHR. 4. These results show that the density of Ca2+ channels of the L-type increases with the worsening of hypertension in SHR. The observation of a different sensitivity to hypertension of Ca2+ channels located in the various portions of the nephron indicates the usefulness of light microscope autoradiography for assessing hypertension-related changes of Ca2+ channels in the kidney.
Amenta
F
F
Sezione di Anatomia Umana, Istituto di Farmacologia, Universita di Camerino, Italy.
Liu
A
A
Sabbatini
M
M
D000818:Animals; D001345:Autoradiography; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; C038806:1,4-dihydropyridine; D009529:Nicardipine