Resetting blood pressure in spontaneously hypertensive rats. The role of bradykinin.
Brief angiotensin-converting enzyme (ACE) inhibition in young spontaneously hypertensive rats (SHR) causes a persistent reduction in blood pressure. Bradykinin accumulation may contribute to these long-term effects, and to test this hypothesis we studied the consequences of bradykinin B2 receptor antagonism during ACE inhibitor treatment in young SHR. Male SHR were treated from 6 to 10 weeks of age with water, ramipril (1 mg/kg per day), Hoe 140 (0.5 mg/kg per day), or both ramipril and Hoe 140. Systolic blood pressure and body weight were measured each week from 6 to 20 weeks of age. During treatment, Hoe 140 treatment resulted in lower blood pressures than in controls. Rampiril caused a larger fall in blood pressure over the same period. The ramipril plus Hoe 140 group had the lowest blood pressures of any group during treatment. After treatment, the blood pressure of Hoe 140-treated SHR was similar to that of untreated SHR. After ramipril, blood pressure rose but plateaued significantly below values in controls. In contrast, withdrawal of combined ramipril and Hoe 140 treatment caused a rapid rise of systolic blood pressure to levels significantly higher than in ramipril-treated SHR but less than in controls. The antihypertensive effects of Hoe 140 during the development of genetic hypertension may represent a direct effect of the drug or some alteration in the normal relation between bradykinin and blood pressure. The antagonism by Hoe 140 of the long-term blood pressure reduction after ramipril withdrawal indicates that the persistent effects of ACE inhibitors may in part be due to the accumulation of bradykinin during a critical stage of development.
Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
J B
JB
O'Sullivan
S B
SB
Harrap
D000375:Aging / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D008297:Male; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; C065679:icatibant; D017257:Ramipril; D001920:Bradykinin