Metabolic effects of isradipine as monotherapy or in combination with pindolol during long-term antihypertensive treatment.
OBJECTIVE
To evaluate the effects of isradipine alone and in combination with pindolol on glucose and lipid metabolism during long-term antihypertensive therapy.


METHODS
Open long-term study with parallel groups.


METHODS
Kungsgärdet Geriatric Hospital, Uppsala, a tertiary referral hospital.


METHODS
Twenty-six untreated hypertensive subjects.


METHODS
After 4 weeks on placebo, isradipine was titrated up to 10 mg daily to achieve appropriate blood pressure control (n = 11). If this failed, 5-10 mg pindolol was added. The treatments were continued for 2 years.


METHODS
Blood pressure, lipoprotein measurements, intravenous glucose tolerance test, hyperinsulinaemic euglycaemic clamp, HbA1c, body weight.


RESULTS
Treatment with isradipine alone caused a sustained reduction in blood pressure (-22/-10 mm Hg, P < 0.01), but an increase in body weight (+2.2 kg, P < 0.05) and HbA1c (+1.5%; P < 0.001) were also noted. Addition of pindolol resulted in a similar degree of blood pressure reduction and weight gain, whilst HbA1c was less affected (+1.0%; P < 0.05, compared to isradipine alone). Insulin sensitivity became impaired in both groups (-1.2 to -1.5 mg kg-1 min-1; P < 0.01 for M-value at hyperinsulinaemic clamp) but after adjustment for the change in body weight the impairment was only significant (P < 0.01) in the group with combined treatment. The combined treatment also resulted in an increase in very-low-density-lipoprotein (VLDL) triglycerides (+ 0.37 mmol L-1; P < 0.05).


CONCLUSIONS
The hypotensive effect of isradipine was sustained during long-term use but was associated with weight gain and an impaired glucose control. When isradipine was combined with pindolol there was also a reduction in insulin sensitivity and an increase in VLDL triglycerides, possibly as effects of the beta-adrenergic blockade.
Department of Cardiology, University Hospital, Uppsala, Sweden.
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Lind
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Berne
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Pollare
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Lithell
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D006441:Hemoglobin A / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D017275:Isradipine / Q000494:pharmacology* / Q000627:therapeutic use; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010869:Pindolol / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D008074:Lipoproteins; D006441:Hemoglobin A; D010869:Pindolol; D017275:Isradipine