Cardiovascular effects after the intracerebroventricular administration of peptide and nonpeptide angiotensin antagonists in Dahl salt-sensitive rats

Cardiovascular responses after the central blockade of the brain angiotensin system with peptide or nonpeptide angiotensin II analogs in conscious, freely moving hypertensive Dahl salt-sensitive (DS/JR) rats were measured. Four-week-old animals were maintained on an 8% salt diet until experimentation at 7 weeks of age. At the time of experimentation, mean arterial pressures were 176 ± 6 mm Hg. The i.c.v. administration of 20 μg of the peptide analog sarcosine¹, threonine⁸-angiotensin II (sarthran) resulted in a significant bradycardic response (~17% decrease in H.R. peaking at 8 min after injection) without a significant change in blood pressure. Central administration of the AT₁ antagonist losartan (10 μg) or of the AT₂ antagonist PD 123319 (10 μg) was without effect. The peptide and nonpeptide analogs differed in their ability to inhibit central angiotensin II (10 ng)-induced pressor and dipsogenic responses. PD 123319 (10 μg) had no effect on the pressor and dipsogenic responses, whereas losartan (10 μg) and sarthran (20 μg) inhibited both responses for 85 ± 17 and 29 ± 3 min, respectively. The effect of preblocking either the AT₁ or the AT₂ receptors on the sarthran-induced bradycardia was also determined. Preblocking with either losartan (10 μg) or PD 123319 (10 μg) inhibited the bradycardic response by ~45%, which suggests that both receptor subtypes are involved in the central cardiovascular responses in the DS/JR rat and that, because it was attenuated by pure antagonists, the response to sarthran may be mediated by its agonist actions. The absence of a significant depressor response after the i.c.v. administration of the peptide or nonpeptide analogs argues against a significant role for the brain angiotensin system in the maintenance of hypertension in the Dahl salt-sensitive rat model.