Ohbu K, Kaskel F J, Kinoshita S, Felder R A
Department of Pediatrics, Kurume University School of Medicine, Japan.
Am J Physiol. 1995 Jan;268(1 Pt 2):R231-5. doi: 10.1152/ajpregu.1995.268.1.R231.
We have previously reported a defect in the coupling of the renal dopamine-1 receptor (D1) to adenylate cyclase (AC) in the proximal convoluted tubule (PCT) of the spontaneously hypertensive rat (Okamoto-Aoki strain). To determine if this defect is present in another model of hypertension, we microdissected PCTs from Dahl salt-sensitive (DSS) and Dahl salt-resistant (DSR) rats on low- or high-NaCl diet. The ability of two selective D1 agonists, fenoldopam and SND-919-C12, and forskolin to stimulate AC activity in PCT was determined in each of the four groups of rats. Fenoldopam (10(-7) M) and SND-919-C12 (10(-6) M) failed to stimulate AC activity in the PCT of DSS rats whether on a low- or high-NaCl diet. In DSR rats, however, both fenoldopam and SND-919-C12 stimulated AC activity by 289-320% and 220-270%, respectively, whether on a low- or high-NaCl intake. Forskolin (10(-5) M), which directly stimulates AC activity, increased AC activity in all four groups. These studies show that in DSS rats the D1 receptor in the PCT fails to respond to D1 agonists. This defect is not a consequence of the hypertension because it was present in the DSS rats on a low-salt diet and before blood pressure elevation.
我们先前曾报道，自发性高血压大鼠（冈本 - 青木品系）近曲小管（PCT）中肾多巴胺 -1 受体（D1）与腺苷酸环化酶（AC）的偶联存在缺陷。为了确定这种缺陷是否存在于另一种高血压模型中，我们从食用低或高氯化钠饮食的 Dahl 盐敏感（DSS）大鼠和 Dahl 盐抵抗（DSR）大鼠中显微解剖出 PCT。在四组大鼠的每一组中，测定了两种选择性 D1 激动剂非诺多泮和 SND - 919 - C12 以及福司可林刺激 PCT 中 AC 活性的能力。无论食用低或高氯化钠饮食，非诺多泮（10^(-7) M）和 SND - 919 - C12（10^(-6) M）均未能刺激 DSS 大鼠 PCT 中的 AC 活性。然而，在 DSR 大鼠中，无论低或高氯化钠摄入量，非诺多泮和 SND - 919 - C12 分别刺激 AC 活性提高了 289 - 320%和 220 - 270%。直接刺激 AC 活性的福司可林（10^(-5) M）在所有四组中均增加了 AC 活性。这些研究表明，在 DSS 大鼠中，PCT 中的 D1 受体对 D1 激动剂无反应。这种缺陷不是高血压的结果，因为它存在于低盐饮食的 DSS 大鼠中以及血压升高之前。
