1. Renal alpha 1- and alpha 2-adrenoceptors were characterized in the New Zealand strain of genetically hypertensive (GH) rat and the Otago random-bred albino normotensive (NT) control rat at 4 and 12 weeks of age with [3H]-prazosin and [3H]-rauwolscine. 2. At 4 weeks of age, the density of alpha-adrenoceptors in NT and GH rats was similar to both the alpha 1- (193 +/- 11 vs 163 +/- 14 fmol mg-1 protein) and alpha 2- (347 +/- 34 vs 319 +/- 41 fmol mg-1 protein) adrenoceptor. At 12 weeks of age, GH rats had a greater density of renal alpha 1- (152 +/- 27 vs 238 +/- 17 fmol mg-1 protein) and alpha 2- (175 +/- 42 vs 350 +/- 23 fmol mg-1 protein) adrenoceptors compared to the NT rats. 3. Pre-incubation of kidneys from GH rats (12 weeks of age) with 1 and 10 microM clonidine decreased the density of receptors identified by unlabelled clonidine displacement of [3H]-rauwolscine to 77% and 56% of control. Pre-incubation with adrenaline, 2,6 dimethylclonidine or phenylephrine failed to alter binding. 4. Pre-incubation of kidneys from NT rats (12 weeks) or young GH rats (4 weeks) with 10 microM clonidine failed to alter displacement of [3H]-rauwolscine by unlabelled clonidine. 5. These studies demonstrate that in another strain of hypertensive rat, the GH rat, alpha 2-adrenoceptor density is increased as compared to the normotensive control at 12 but not 4 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)
In animal studies, acute interruption of the activity of renal alpha-1 adrenoceptors by renal denervation results in an increase in sodium and water excretion. Chronic selective blockade of alpha-1 adrenoceptors by prazosin in clinical practice has been associated with sodium retention, however. Previous studies in the authors' laboratory using chronic alpha-1 blockade in the rat have demonstrated a decreased ability to excrete a saline load. Therefore, the authors determined the effect of chronic selective alpha-1 adrenoceptor blockade with prazosin in eight healthy volunteers. Volunteers underwent a water load to establish a water diuresis, followed by a modest saline load using intravenous saline (0.9% NaCl). This experimental protocol was repeated after four weeks of prazosin therapy (5 mg twice daily). Prazosin failed to alter body weight (73.6 +/- 4.2 versus 74.5 +/- 4.1 kg, expressed as mean +/- standard error), mean blood pressure (86.7 +/- 2.7 versus 84.7 +/- 2.3 mm Hg), creatinine clearance (127.0 +/- 8.5 versus 133.4 +/- 12.0 mL/min), renal blood flow as measured by para-aminohippurate clearance (1202 +/- 88 versus 1175 +/- 69 mL/min) and the 24-hour sodium excretion (115 +/- 11 versus 128 +/- 19 mmol). In the presence of the experimentally induced saline load, chronic prazosin treatment was associated with a decreased free water clearance (e.g., hour 3, 7.8 +/- .7 versus 6.3 +/- 2.0 mL/min; P < or = .05) and fractional excretion of sodium (e.g., hour 3, 1.48 +/- .10 versus 1.15 +/- .13; P < or = .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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