Impaired baroreflex control of heart rate in high-renin renal hypertension

Abstract

The reflex responses of heart rate (HR) to bolus injection and infusion of phenylephrine and nitroglycerine were studied in rats with one-kidney, one clip (1-K, 1C) hypertension and hypertension produced by aortic ligation. Rats with mild 1-K, 1C hypertension (147 ± 4 mmHg) and a normal renin-angiotensin system (RAS) activity had normal bradycardic and tachycardic responses, whereas rats with severe hypertension (208 ± 3 mmHg) and over-active RAS showed impairment (70-80%) of the responses. After 12 days of aortic ligation rats with mild (146 ± 2 mmHg) and severe (175 ± 3 mmHg) hypertension exhibited overactivity of the RAS and marked impairment of the baroreflex control of HR. Normalization of RAS activity in rats with mild hypertension 60 days after aortic ligation, coincided with normalization of the bradycardic responses, whereas the abnormality persisted in those rats with severe hypertension in which hyperactivity of RAS also persisted. The response to 20-s carotid occlusion and the HR responses to electrical stimulation of the vagus nerve were normal in rats with renal hypertension, 12 days after aortic ligation. An ether inhalation test produced a marked reduction of 60% in the HR of control awake rats accompanied by a 46 ± 5 mmHg increase in blood pressure. Reflex pathways other than those through the baroreceptors were largely responsible for the bradycardia since responses remained unchanged in rats with sino-aortic denervation (SAD) or when the pressure increase was prevented by phenoxybenzamine administration. Rats with renal hypertension and overactivity of RAS showed normal bradycardia responses to the ether inhalation test while the bradycardic responses to phenylephrine were depressed by 67%. These data indicate the existence of a close correlation between overactivity of RAS and impairment of the baroreflex control of HR in rats with renal hypertension. Moreover, they indicate that the abnormality is specific for the baroreflex since the response to ether inhalation test remained unchanged.