Ohbu K, Hendley E D, Yamaguchi I, Felder R A
Department of Pediatrics & Child Health, Kurume University School of Medicine, Japan.
Hypertension. 1993 Apr;21(4):485-90. doi: 10.1161/01.hyp.21.4.485.
Renal dopamine-1 (DA-1) receptors are involved in the regulation of sodium transport in several nephron segments, including the proximal convoluted tubule (PCT). DA-1 receptors in the PCT and cortical collecting duct of normotensive rats are linked to the stimulation of adenylyl cyclase (AC). We have reported a defect in the DA-1 receptor/AC coupling in the PCT of the spontaneously hypertensive rat (SHR) of the Okamoto-Aoki strain. Hyperactivity and hypertension are both expressed in the SHR. To determine if the DA-1 receptor coupling defect is associated with hyperactivity or hypertension, we studied the DA-1 receptor in the PCT of two new inbred rat strains derived from the SHR: the hyperactive WKHA and the hypertensive WKHT rat. Tail-cuff blood pressures taken at 4 weeks indicated that WKHT rats were not hypertensive (86 +/- 3 mm Hg, n = 6), whereas at 12 weeks systolic pressures in both SHR and WKHT rats exceeded 150 mm Hg. Hyperactivity, however, was noted in WKHA rats even at this early age. Basal AC activity was similar in WKHA and WKHT PCT in either age group. In the older rats, the DA-1 agonist fenoldopam (10(-7) mol/L) stimulated AC activity in WKHA (70.6 +/- 16.1 fmol per 3 mm PCT per 20 minutes, n = 3) but not in WKHT PCT (43.3 +/- 5.3 fmol per 3 mm PCT per 20 minutes, n = 4). Gpp(NH)p (10(-5) mol/L), a nonhydrolyzable GTP analogue, stimulated AC activity to a similar extent in WKHA and WKHT PCT.(ABSTRACT TRUNCATED AT 250 WORDS)
肾多巴胺-1（DA-1）受体参与调节包括近端曲管（PCT）在内的多个肾单位节段的钠转运。正常血压大鼠的PCT和皮质集合管中的DA-1受体与腺苷酸环化酶（AC）的刺激有关。我们报道了冈本-青木品系自发性高血压大鼠（SHR）的PCT中DA-1受体/AC偶联存在缺陷。SHR表现出多动和高血压。为了确定DA-1受体偶联缺陷是否与多动或高血压有关，我们研究了源自SHR的两种新的近交系大鼠品系的PCT中的DA-1受体：多动的WKHA和高血压的WKHT大鼠。4周时测量的尾袖血压表明，WKHT大鼠没有高血压（86±3 mmHg，n = 6），而在12周时，SHR和WKHT大鼠的收缩压均超过150 mmHg。然而，即使在这个早期阶段，WKHA大鼠也表现出多动。在任何一个年龄组中，WKHA和WKHT的PCT中的基础AC活性相似。在老年大鼠中，DA-1激动剂非诺多泮（10^(-7) mol/L）刺激WKHA的AC活性（每3 mm PCT每20分钟70.6±16.1 fmol，n = 3），但不刺激WKHT的PCT（每3 mm PCT每20分钟43.3±5.3 fmol，n = 4）。不可水解的GTP类似物Gpp(NH)p（10^(-5) mol/L）在WKHA和WKHT的PCT中刺激AC活性的程度相似。（摘要截断于250字）
