Effects of Beta-Adrenergic Receptor Blocking Agents on Blood Pressure in Conscious Hypertensive Rats

Abstract

Abstract-The effects of beta-adrenergic receptor blocking agents administered i.v. on the blood pressure in conscious spontaneously hypertensive rats (SHR), renal hyper tcnsive rats (RHR) and normotensive Wistar strain rats (NR) were studied. dl-Pro pranolol and dI-YB-2, I mg/kg i.v., caused a sustained rise in blood pressure in SHR and RHR.The maximum response of each beta-blocking agent after phentolamine, 10 mg/kg i.v., in SHR and RHR was significantly larger than that in NR. The po tency ratio for the hypertensive activities of the I and d-isomers of propranolol and YB-2 was similar to the ratio of their beta-blocking activities.The pressor effects of the beta-blocking agents after phentolamine were significantly inhibited by adre nalectomy, reserpinization and pretreatment with hexamethonium. The results sug gest that the pressor effect of the beta-blocking agents may be due to their beta-block ing activities and the unmasking of alpha-receptor activities of the blood vessels. Furthermore, the greater pressor effect of the agents observed in hypertensive rats is attributed to a greater activity of the sympathetic nervous system in these rats as com pared to normotensive rats.The antihypertensive activity of propranolol and other beta-adrenergic receptor block ing agents in certain hypertensive patients has been reported (I-8), but the activity has been observed only after prolonged oral administrations in relatively large doses. How ever, exact mechanism involved in the antihypertenseve activity of the agents is not clear.The activity of beta-blocking agents has not been confirmed in commonly used hyper tensive animals (9, 10). Recently, Roba et al. reported that beta-blocking agents adminis tered orally caused a significant fall in blood pressure in unanesthetized spontaneously hypertensive rats and the order of hypotensive potency was unrelated to the beta-block ing activity (I I).In the present study, the effects of intravenously administered beta-blocking agents on blood pressure and heart rate in conscious spontaneously hypertensive rats and renal hypertensive rats were investigated utilizing the direct cannulation method into the abdomi nal aorta via the median coccygeal artery and the results were compared with those observed in normotensive Wistar strain rats. The difference in the cardiovascular responsiveness to beta-blocking agents, and that in the sympathetic nervous activity to the cardiovascular system between hypertensive and normotensive rats was also Studied.

PREVENTION AND REVERSAL OF ISOLATION-INDUCED SYSTOLIC ARTERIAL HYPERTENSION IN RATS BY TREATMENT WITH Β-Adrenoceptor ANTAGONISTS

“…In mature spontaneously hypertensive rats, propranolol has been reported to lower (Roba, Lambelin & de Schaepdryver, 1972) or to have no effect on (Forman & Mulrow, 1974, Buniag, 1977 systolic BP, and to lower (Garvey & Ram, 1975) to raise (Nakao, Kato & Takagi, 1975) or to have no effect on (Weiss, Lundgren & Folkow, 1974;Conway, Darwin Hilditch, Loveday & Reeves, 1975) mean arterial BP. Furthermore, it has been found that pretreatment with propranolol may either not affect (Frohlich & Pfeffer, 1975) or may prevent (Weiss et al, 1975) the development of the spontaneous hypertension.…”

Antihypertensive Activity of Orally Administered Methyl O-(4-Hydroxy-3-Methoxycinnamoyl) Reserpate (CD-3400) in Conscious Hypertensive Rats

“…Blood pressure and heart rate of spontaneously hypertensive rats (SHR) were measured according to the method described by Nakao et al (2 namoyl)reserpate (CD-3400), as shown in Fig. 1, is a light yellow powder which is in soluble in water and was crystallized from dioxane.…”

Comparison of the Anti‐hypertensive Response to Β‐adrenoceptor Blocking Drugs in Intact and Adrenal‐demedullated Spontaneously Hypertensive Rats

“…Although the spontaneously hypertensive (SH) rat has been used extensively to study the aetiology of hypertensive disease and to investigate the mechanisms responsible for mediating the effects of clinically useful anti-hypertensive drugs, it, like other laboratory animal preparations, has proved to be of limited value in studying the antihypertensive properties of,-adrenoceptor blocking drugs (see review by Buckingham & Hamilton, 1979). It is feasible that the ability of these drugs to stimulate adrenal catecholamine release (Nakano & Kusakari, 1965;Kayaalp & Kiran, 1966;Kayaalp & Turker, 1967;Dasgupta, 1968;Yamamoto & Sekiya, 1969;Regoli, 1970;Eliash & Weinstock, 1972;Regoli, Regoli & Gysling, 1972;Nakao, Kato & Takagi, 1975) could be responsible for masking their blood pressure lowering activity in conscious animals. In this respect, unilateral adrenalectomy and contralateral adrenal demedullation has been shown to unmask 0007-1188/80/040667-10 $01.00 a blood pressure lowering effect of oxprenolol in onekidney renal hypertensive rats (Brunner & Hedwall, 1970), and to augment the anti-hypertensive response to pindolol in deoxycorticosterone acetate (DOCA)/ saline-treated rats (Buckingham, Hamilton & Robson, 1978).…”