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Volume 2, Number 2, June 2001
Effects of telmisartan, hydrochlorothiazide and their combination on blood pressure and renal excretory parameters in spontaneously hypertensive rats
Wolfgang Wienen, Hans-Joachim Schierok The effects of telmisartan
and hydrochlorothiazide (HCTZ) alone and in combination on blood pressure (BP) and
renal excretory function were investigated in male spontaneously hypertensive rats
(SHR) after oral administration for five consecutive days. Four treatments were
studied: vehicle (0.5% Natrosol™), telmisartan 3 mg/kg, HCTZ 10 mg/kg,
and telmisartan 3 mg/kg+ HCTZ 10 mg/kg. The effects on BP and heart rate were studied
in 40 SHRs (10 animals per group) using an implanted telemetry device. Renal excretory
function was assessed in 76 SHRs (18 animals per group, of which nine were used
for urine sampling and nine for blood sampling).
The telmisartan/HCTZ combination
produced the greatest reductions in trough DBP (–44±1.5 mmHg), SBP (–60±1.9
mmHg) and mean BP (mBP; –53±1.7 mmHg) after five days of therapy (p<0.05
vs. vehicle and vs. telmisartan). Telmisartan monotherapy also decreased DBP, SBP
and mBP significantly (p<0.05), but only minor BP fluctuations occurred in SHRs
receiving HCTZ or vehicle. Telmisartan/HCTZ elevated heart rate by approximately
12 beats per minute (p<0.05 vs. control). Significant increases in urine volume
and Na+, Cl–, K+, creatinine and glucose
excretion were observed with HCTZ treatment (p<0.01). Telmisartan/HCTZ also promoted
renal water and electrolyte excretion (p<0.01); the diuretic effect appeared
to be greater with the combination than with HCTZ alone, and there was some attenuation
of urinary K+ loss. Elevated blood urea nitrogen levels were observed
only in HCTZ-treated SHRs. These results indicate that the antihypertensive efficacy
of telmisartan in SHRs is augmented by co-administration with HCTZ. The combination
did not affect renal excretory function, with the exception of an increase in blood
urea nitrogen and a possible amelioration of HCTZ-related K+ depletion. JRAAS 2001;2:123-128. View full PDF article (open in new window)
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