Effects of telmisartan, hydrochlorothiazide and their combination on blood pressure and renal excretory parameters in spontaneously hypertensive rats.
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.
Wienen
W
W
Department of Pharmacological Research, Boehringer Ingelheim, Biberach an der Riss, Germany. wolfgang.wienen@bc.boehringer-ingelheim.com
Schierok
H J
HJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004232:Diuretics; D004359:Drug Therapy, Combination; D006339:Heart Rate / Q000187:drug effects; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*; D000077333:Telmisartan; D014556:Urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D000077333:Telmisartan