[Binding sites of imidazolines. Study with (3H)-idazoxan in renal cortex of Sabra salt-sensitive (SBH) and salt-resistant (SBN) rats].
Imidazoline binding sites have been characterized in organs modulating blood pressure, such as brain and kidney with (3H)-p-aminoclonidine and (3H)-Idazoxan respectively. However, the pharmacological characteristics of the imidazoline-preferring binding sites differ considerably depending on the species investigated and the radioligand used. Little is known about the physiological relevance of the non-adrenergic (3H)-idazoxan binding sites. As some imidazolines and certain alpha-adrenoceptor agonists possess antihypertensive activity, an alteration of these binding sites should be considered as a possible causes in the development of hypertension. In the present study, we performed binding studies with the imidazoline ligand (3H)-idazoxan in renal cortex of hypertensive salt-sensitive (SBH) and normotensive salt-resistant (SBN) Sabra rats. (3H)-idazoxan binding capacities were higher in SBH than in SBN rats. Competition studies have shown for (3H)-idazoxan specific binding non-adrenergic characteristics exclusively. In these both substrains, (3H)-idazoxan binding exhibit pharmacological profile of imidazoline binding sites. However, theses sites have also high affinity for guanidino compounds and amiloride. Surprisingly, amiloride and some analogues were significantly more potent in SBN than in SBH rats. From this study, it is difficult to elucidate the physiological role of imidazoline binding sites in renal cortex. However, differences observed between SBN and SBH suggest that these sites may play a role in the development of hypertension in Sabra rats.
Qing
W
W
U 7 INSERM/UA 318 CNRS, département de pharmacologie, hôpital Necker, Paris.
Ben-Ishay
D
D
Dausse
J P
JP
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D004146:Dioxanes / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced; D019329:Idazoxan; D007093:Imidazoles / Q000378:metabolism*; D007672:Kidney Cortex / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051381:Rats; D012965:Sodium Chloride / Q000009:adverse effects
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D012965:Sodium Chloride; D019329:Idazoxan