Acute AT1 receptor blockade does not improve the depressed baroreflex in rats with chronic renal hypertension.
To assess the role of angiotensin II in the sensitivity of the baroreflex control of heart rate (HR) in normotensive rats (N = 6) and chronically hypertensive rats (1K1C, 2 months, N = 7), reflex changes of HR were evaluated before and after (15 min) the administration of a selective angiotensin II receptor antagonist (losartan, 10 mg/kg, iv). Baseline values of mean arterial pressure (MAP) were higher in hypertensive rats (195 +/- 6 mmHg) than in normotensive rats (110 +/- 2 mmHg). Losartan administration promoted a decrease in MAP only in hypertensive rats (16%), with no changes in HR. During the control period, the sensitivity of the bradycardic and tachycardic responses to acute MAP changes were depressed in hypertensive rats (approximately 70% and approximately 65%, respectively) and remained unchanged after losartan administration. Plasma renin activity was similar in the two groups. The present study demonstrates that acute blockade of AT1 receptors with losartan lowers the MAP in chronic renal hypertensive rats without reversal of baroreflex hyposensitivity, suggesting that the impairment of baroreflex control of HR is not dependent on an increased angiotensin II level.
Farah
V M
VM
Divisão de Experimentação e Unidade de Hipertensão, Instituto do Coração - InCor, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo.
Moreira
E D
ED
Ushizima
M
M
Cestari
I A
IA
Irigoyen
M C
MC
Krieger
E M
EM
D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017704:Baroreflex / Q000187:drug effects*; D001919:Bradycardia / Q000188:drug therapy; D002908:Chronic Disease; D006339:Heart Rate / Q000187:drug effects*; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013610:Tachycardia / Q000188:drug therapy
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D019808:Losartan