Renal Dopamine-1 Receptors in Hypertensive Inbred Rat Strains With and Without Hyperactivity

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1993-04, Vol.21 (4), p.485-490
• Main Authors: Ohbu, Keizou, Hendley, Edith D, Yamaguchi, Ikuyo, Felder, Robin A
• Format: Article
• Language: English
• Subjects: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - analogs & derivatives; 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology; Adenylyl Cyclases - metabolism; Aging - metabolism; Animals; Arterial hypertension. Arterial hypotension; Benzazepines - analogs & derivatives; Benzazepines - metabolism; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure; Cardiology. Vascular system; Colforsin - pharmacology; Dopamine Agents - pharmacology; Experimental diseases; Fenoldopam; Guanylyl Imidodiphosphate - pharmacology; Hypertension - metabolism; Hypertension - physiopathology; Iodine Radioisotopes; Kidney - metabolism; Kidney Cortex - metabolism; Kidney Tubules, Collecting - metabolism; Kidney Tubules, Proximal - metabolism; Kinetics; Male; Medical sciences; Motor Activity - drug effects; Nephrons - metabolism; Radioligand Assay; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Receptors, Dopamine D1 - metabolism; Sodium - metabolism
• ISSN: 0194-911X; 1524-4563
• 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 SHRthe hyperactive WKH A 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 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 tool per 3 mm PCT per 20 minutes, n =4). Gpp(NH)p (10 mol/L), a nonhydrolyzable GTP analogue, stimulated AC activity to a similar extent in WKHA and WKHT PCT. Forskolin (10 mol/L) also stimulated AC activity to a similar extent in PCT from both strains. Similar results were obtained in the younger, prehypertensive rats. The specific binding of the DA-1 antagonist I-Sch 23982 was concentration dependent and saturable in both strains. The dissociation constant (Kd, and maximum receptor density (Bmax) were similar in WKHA PCT (23.9±1.7 nraol/L and 0.52 ±0.04 pmol/mg protein, n=5) and WKHT PCT (23.8±3.8 nmol/L and 0.58±0.14 pmol/mg protein, n=5). These data demonstrate that the coupling defect between the DA-1 receptor and AC in the PCT from these new inbred rat strains is associated with the hypertensive phenotype. The DA-1 receptor in PCT may be important in the pathogenesis of genetic hypertension.