Dopamine D2-like receptors in the kidney of spontaneously hypertensive rats: a radioligand binding assay and light microscope autoradiography study.
1. Dopamine D2-like receptors were investigated in sections of kidney from male spontaneously hypertensive rats (SHRs) at 6 and 14 weeks of age using radioligand binding assay and autoradiographic techniques with [3H]-spiperone as a ligand. 2. Systolic blood pressure values were slightly higher in 6-week-old SHRs in comparison with age-matched normotensive Wistar-Kyoto (WKY) rats and considerably higher in 14-week-old SHRs in comparison with the other groups investigated. Renal dopamine levels were higher in SHRs aged 6 and 14 weeks in comparison with age-matched WKY rats. Noradrenaline concentrations were similar in 6-week-old SHRs and normotensive WKY rats, and increased slightly in SHRs aged 14 weeks. 3. The density of [3H]-spiperone binding sites was similar in SHRs and WKY rats at 6 weeks of age, and decreased in SHRs at 14 weeks in comparison with age-matched normotensive animals. Light microscope autoradiography revealed the accumulation of silver grains in the tunica adventitia, in the adventitia-media border of intrarenal arteries and within cortical tubules. A few specific silver grains were also developed in the glomerular tuft. No changes in the density and pattern of silver grains were noticeable between SHRs and WKY rats at 6 weeks of age, whereas a reduction in silver grains largely affecting vascular binding sites was observed at 14 weeks of age. 4. Renal denervation considerably decreased the density of [3H]-spiperone binding sites in sections of rat kidney, with an almost complete loss of vascular binding sites. 5. The above findings indicate the occurrence of a decrease of dopamine D2-like receptors in the kidney of SHRs with the progress of hypertension. Dopamine D2-like receptors which are mainly prejunctional are involved in the modulation of sympathetic neurotransmission in the kidney. The loss of these receptors in SHRs may contribute to the pathophysiology of hypertension.
Barili
P
P
Dipartimento di Scienze Farmacologiche e Medicina Sperimentale, Università di Camerino, Italy.
Fringuelli
C
C
Baldoni
E
E
Mignini
F
F
Zaccheo
D
D
Amenta
F
F
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013134:Spiperone / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D017448:Receptors, Dopamine D2; D013134:Spiperone; D004298:Dopamine; D009638:Norepinephrine