Chronic prazosin attenuates the natriuretic response to a modest saline load in anaesthetized rats

Abstract

The effect of chronic prazosin pretreatment (3 days) on the ability to excrete a modest saline load (i.v. saline, 0.097 ml min−1) was studied in the anaesthetized rat. Three days before the experiment, the drinking water was replaced with 0.5% dextrose (control), 0.015 mg ml−1 prazosin in 0.5% dextrose (low dose) or 0.15 mg ml−1 prazosin in 0.5% dextrose (high dose). The selectivity of the prazosin for α1‐adrenoceptors was evaluated in pithed rats. The pressor response to phenylephrine was partially attenuated by the low dose of prazosin and completely attenuated by the high dose of prazosin. The pressor response to clonidine was slightly decreased by the 3 day prazosin pretreatment indicating a selectivity for α1‐adrenoceptors. In rats pretreated with the low dose of prazosin, there was a significant decrease in sodium and water, but not potassium excretion as compared to the control group. Captopril failed to alter these effects of the low dose of prazosin. Blood pressure and creatinine clearance were the same in both groups. In rats pretreated with the high dose of prazosin, there was a further decrease in sodium and water but not potassium excretion. However, this dose of prazosin also significantly decreased blood pressure and increased creatinine clearance. A decrease in renal perfusion pressure with an aortic clamp to the same level as that observed with the high prazosin dose also decreased sodium and water but not potassium excretion. The decrease in sodium and water excretion was not as great as that observed with the high dose of prazosin. The results indicate that chronic α1‐adrenoceptor blockade with prazosin attenuates the ability to excrete a saline load in a dose‐related manner. Whether this inability to excrete a saline load is analogous to the sodium and water retention observed with the clinical use of prazosin remains to be determined.

The role of the peripheral sympathetic nervous system in the natriuresis following central administration of an I1 imidazoline agonist, moxonidine

“…administration of I-imidazoline receptor agonists has not been defined. Since the activation of the peripheral ax-adrenoceptor (Penner & Smyth, 1988) Clonidine and structurally related compounds have been shown to lower blood pressure through stimulation of imidazoline receptors located centrally (Feldman et al, 1990;Tibirica et al, 1991;Gomez et al, 1991). Clonidine, through what now appears to be imidazoline receptors located in the ventrolateral medulla, has been found to lower blood pressure in a number of different species (Gillis et al, 1985;Sinha et al, 1985;McAuley et al, 1988;Feldman et al, 1990).…”

“…Intracerebroventricular moxonidine with or without intravenous prazosin: Prazosin (0.15 mg kg-') or saline vehicle was administered intravenously at the beginning of the stabilization period in a volume of 0.15 ml over 30 s (Penner & Smyth, 1988). The i.c.v.…”

Peripheral and Central Imidazoline Receptor‐Mediated Natriuresis in the Rata

“…The density of renal α 1 ‐ and α 2 ‐adrenoceptors had been found to be altered in genetic models of hypertension in rats. 5–8 Subsequent studies established a potential role of these receptors in the modulation of blood pressure through the control of vascular tone and of sodium and water excretion for the α 1 ‐adrenoceptor 9–14 and the α 2 ‐adrenoceptor. 13,15–23 In documenting the function of renal α 2 ‐adrenoceptors, our studies indicated that the observed effects may have been due to activation of more than one receptor type, 24 but it was not clear if this receptor type was an α 2 ‐adrenoceptor subtype or a completely different receptor.…”