Abstract
Aim:
To test the synergistic effects of atenolol and amlodipine on lowering blood pressure (BP) and reducing blood pressure variability (BPV) in 2-kidney, one-clip (2K1C) renovascular hypertensive rats.
Methods:
Forty-eight 2K1C renovascular hypertensive rats were randomly divided into 6 groups. They were respectively given 0.8% carboxymethylcellulose sodium (control), atenolol (10.0 mg/kg), amlodipine (1.0 mg/kg), and combined atenolol and amlodipine (low dose: 5.0+0.5 mg/kg; intermediate dose: 10.0+1.0 mg/kg; high dose: 20.0+2.0 mg/kg). The drugs were given via a catheter in a gastric fistula. BP was recorded for 25 h from 1 h before drug administration to 24 h after administration.
Results:
Compared with BP before medication, all 3 doses of combined atenolol and amlodipine significantly decreased the BP at 24 h after administration, except for the low dose on diastolic BP. Compared with the control group, all 3 doses of combined atenolol and amlodipine significantly reduced the average BP levels for the 24 h period after administration; furthermore, the high and intermediate doses also significantly decreased the BPV levels for the same period. The q values calculated by probability sum analysis for systolic and diastolic BP for the 24 h period after administration were 2.29 and 1.45, respectively, and for systolic and diastolic BPV for the same period they were 1.41 and 1.60, respectively.
Conclusion:
There is significant synergism between atenolol and amlodipine in lowering and stabilizing BP in 2K1C renovascular hypertensive rats.
Similar content being viewed by others
Article PDF
References
Mancia G, Ferrari A, Gregorini L, Parati G, Pomidossi G, Bertinieri G, et al. Blood pressure and heart rate variabilities in normotensive and hypertensive human beings. Circ Res 1983; 53: 96–104.
Su DF, Cerutti C, Barres C, Vincent M, Sassard J . Blood pressure and baroreflex sensitivity in conscious hypertensive rats of Lyon strain. Am J Physiol 1986; 251: H1111–7.
Miao CY, Shen FM, Su DF . Blood pressure variability is increased in genetic hypertension and L-NAME-induced hypertension. Acta Pharmacol Sin 2001; 22: 137–40.
Parati G, Pomidossi G, Albini F, Malaspina D, Mancia G . Relationship of 24-hour blood pressure mean and variability to severity of target-organ damage in hypertension. J Hypertens 1987; 5: 93–8.
Mancia G, Frattola A, Parati G, Santucciu C, Ulian L . Blood pressure variability and organ damage. J Cardiovasc Pharmacol 1994; 24: S6–11.
Su DF, Miao CY . Blood pressure variability and organ damage. Clin Exp Pharmacol Physiol 2001; 28: 709–15.
Du WM, Miao CY, Liu JG, Shen FM, Yang XQ, Su DF . Effects of long-term treatment with ketanserin on blood pressure variability and end-organ damage in spontaneously hypertensive rats. J Cardiovasc Pharmacol 2003; 41: 233–9.
Xie HH, Miao CY, Liu JG, Su DF . Importance of blood pressure variability in organ protection in spontaneously hypertensive rats treated with combination of nitrendipine and atenolol. Acta Pharmacol Sin 2002; 23: 1199–204.
Lu ZA, Xie HH, Xu LP, Yin AF, Miao CY, Su DF . Restoration of arterial baroreflex function contributes to organ protection in spontaneously hypertensive rats treated with long-term hydrochlorothiazide mixture. Clin Exp Pharmacol Physiol 2003; 30: 49–54.
Xie HH, Miao CY, Jiang YY, Su DF . Synergism of atenolol and nitrendipine on hemodynamic amelioration and organ protection in hypertensive rats. J Hypertens 2005; 23: 193–201.
Materson BJ, Reda DJ, Cushman WC, Massie BM, Freis ED, Kochar MS, et al. Single-drug therapy for hypertension in men: a comparison of six antihypertensive agents with placebo: the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. N Engl J Med 1993; 328: 914–21.
The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure, [ published erratum appears in Arch Intern Med 1998; 158: 573] Arch Intern Med 1997; 157: 2413–46.
Guan S, Fox J, Mitchell KD, Navar LG . Angiotensin and angiotensin-converting enzyme tissue levels in two-kidney, one clip hypertensive rats. Hypertension 1992; 20: 763–7.
Jin ZJ . About the evaluation of drug combination. Acta Pharmacol Sin 2004; 25: 146–7.
Su DF, Xu LP, Miao CY, Xie HH, Shen FM, Jiang YY . Two useful methods for evaluating antihypertensive drugs in conscious freely moving rats. Acta Pharmacol Sin 2004; 25: 148–51.
Eisen SA, Miller DK, Woodward RS, Spitznagel E, Przybeck TR . The effect of prescribed daily dose frequency on patient medication compliance. Arch Intern Med 1990; 150: 1881–4.
Sica DA . Fixed-dose combination antihypertensive drugs. Do they have a role in rational therapy? Drugs 1994; 48: 16–24.
Prisant LM . Fixed low-dose combination in first-line treatment of hypertension. J Hypertens 2002; 20: S11–9.
Moser M . Current recommendations for initial therapy in hypertension: are they still valid? Introduction. Am J Hypertens 1998; 11: 69S–72S.
Moser M, Black HR . The role of combination therapy in the treatment of hypertension. Am J Hypertens 1998; 11: 73S–78S.
Shan ZZ, Dai SM, Su DF . Relationship between baroreceptor reflex function and end-organ damage in spontaneously hypertensive rats. Am J Physiol 1999; 277: H1200–6.
Su DF, Miao CY . Reduction of blood pressure variability: a new strategy for treatment of arterial hypertension. Trends Pharmacol Sci 2005; 26: 388–90.
Weir MR . The rationale for combination versus single-entity therapy in hypertension. Am J Hypertens 1998; 11: 163S–169S.
Suzuki H, Moriwaki K, Kanno Y, Nakamoto H, Okada H, Chen XM . Comparison of the effects of an ACE inhibitor and alphabeta blocker on the progression of renal failure with left ventricular hypertrophy: preliminary report. Hypertens Res 2001; 24: 153–8.
Waeber B, Detry JM, Dahlof B, Puig JG, Gundersen T, Hosie J, et al. Felodipine-metoprolol combination tablet: a valuable option to initiate antihypertensive therapy? Am J Hypertens 1999; 12: 915–20.
Menard J . Critical assessment of combination therapy development. Blood Press 1993; 1 Suppl: 5–9.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project supported by the Foundation for the Science and Technology Development of Shanghai (No 04JC14001) and the High Tech Research and Development (863) Program of China (No 2002 AA2Z346C).
Rights and permissions
About this article
Cite this article
Shen, Fm., Xie, Hh., Ling, G. et al. Synergistic effects of atenolol and amlodipine for lowering and stabilizing blood pressure in 2K1C renovascular hypertensive rats. Acta Pharmacol Sin 26, 1303–1308 (2005). https://doi.org/10.1111/j.1745-7254.2005.00185.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2005.00185.x
Keywords
This article is cited by
-
Alteration of serum immunoglobins, C-reactive protein, vitamin D, and electrolyte by atenolol and amlodipine in stress-induced hypertensive rats
Molecular and Cellular Biochemistry (2018)
-
Rodent models of heart failure: an updated review
Heart Failure Reviews (2013)
-
Downregulation of alpha7 nicotinic acetylcholine receptor in two-kidney one-clip hypertensive rats
BMC Cardiovascular Disorders (2012)
-
Effects of allisartan, a new AT1 receptor blocker, on blood pressure and end-organ damage in hypertensive animals
Acta Pharmacologica Sinica (2009)