Antihypertensive agents have different ability to modulate arterial pressure and heart rate variability in 2K1C rats.
We examined the effect of chronic (15 days) administration of antihypertensive agents, from different pharmacologic classes, on arterial pressure (AP) and heart rate variability in two-kidney, one-clip hypertensive (2K1C) rats. The 2K1C rats received by gavage one of the following: water, ramipril, losartan, atenolol, amlodipine, or hydrochlorothiazide. Sham-operated normotensive rats received water. After 15 days of treatment AP was continuously sampled from an indwelling catheter in awake rats during a 2-h period and systolic AP and pulse interval (PI) were submitted to autoregressive spectral analysis with oscillatory components quantified in low (LF: 0.25 to 0.75 Hz) and high (HF: 0.75 to 3.0 Hz) frequency bands. The AP measured by tail-cuff was 170 +/- 2 mm Hg in 2K1C and 131 +/- 3 mm Hg in normotensive rats. Pooled data indicated that all antihypertensive agents reduced the AP of 2K1C rats to 127 +/- 2 mm Hg, whereas 2K1C rats treated with water remained hypertensive (206 +/- 11 mm Hg). Variance of systolic AP was found increased in 2K1C rats treated with water (34 +/- 2 mm Hg2), whereas 2K1C rats treated with ramipril, atenolol, amlodipine, or hydrochlorothiazide presented AP variance similar to normotensive rats (16 +/- 2 mm Hg2). Losartan normalized AP of 2K1C rats but variance of systolic AP remained increased (34 +/- 7 mm Hg2). The 2K1C rats treated with water had increased LF of systolic AP, whereas 2K1C rats treated with losartan showed higher LF of systolic AP and PI. Atenolol presented lower LF and higher HF of PI. In conclusion, losartan normalized AP but did not reduce AP variability, suggesting an autonomic imbalance characterized by higher sympathetic modulation of the cardiovascular system.
Nobre
Fernando
F
Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
da Silva
Carlos Alberto Aguiar
CA
Coelho
Eduardo Barbosa
EB
Salgado
Helio Cesar
HC
Fazan
Rubens
R
D017311:Amlodipine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002319:Cardiovascular System / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D017311:Amlodipine; D001262:Atenolol; D019808:Losartan; D017257:Ramipril