Antihypertensive mechanism of the diuretic muzolimine in mild renal failure. Roles of sodium and cardiovascular norepinephrine responsiveness.
Eighteen patients with mild impairment of renal function (glomerular filtration rate 65 +/- 5 ml/min:m +/- SEM) and hypertension (168/105 +/- 6/3 mmHg) were shown on average to have abnormally increased cardiovascular pressor responsiveness to infused norepinephrine (NE; p less than 0.05), whereas plasma and urinary NE, exchangeable body sodium and blood-volume did not differ significantly from normal. A slightly increased pressor responsiveness to angiotensin II was associated with a tendency to low plasma renin activity (PRA). Compared to placebo conditions, treatment with the loop-diuretic muzolimine in a mean dose of 35 +/- 2 mg/day for six weeks decreased blood-pressure and exchangeable sodium (p less than 0.05), and NE pressor responsiveness was restored to normal values, whilst plasma and urinary NE were not significantly changed. This was consistent with improvement of the initially abnormal relationship between NE levels and NE responsiveness factors. In contrast, the pressor dose of angiotensin II and PRA were increased to an approximatively similar extent during muzolimine treatment. These observations suggest that removal of body sodium and a decrease in NE reactivity without an equivalent increase in sympathetic nervous activity may be important complementary factors in the antihypertensive mechanisms of diuretic treatment in patients with mild renal functional impairment.
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001810:Blood Volume / Q000187:drug effects; D005260:Female; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009156:Muzolimine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D012964:Sodium / Q000502:physiology*
D011720:Pyrazoles; D009156:Muzolimine; D000804:Angiotensin II; D012964:Sodium; D012083:Renin; D009638:Norepinephrine