Acute blood pressure and urinary responses to single dose combinations of captopril and diuretics in conscious spontaneously hypertensive rats

Abstract

The present studies involved oral administration of captopril alone or in combination with individual diuretics in conscious, freely-moving spontaneously hypertensive rats (SHR). Both blood pressure (BP) and urinary fluid and electrolyte excretion were concomitantly measured. Captopril, 10 mg kg-1, caused a decrease in BP (-18 +/- 3 mm Hg) which was not significantly different from control (-10 +/- 2 mm Hg). Diuretics alone also failed to alter BP. However the BP-lowering effect of captopril was readily potentiated by concomitant administration of a single oral dose of frusemide (10 and 30 mg kg-1) in proportion to the magnitude of urinary loss. Hydrochlorothiazide at 1 and 3 mg kg-1 oral and metolazone at 0.3 and 1 mg kg-1 oral induced fluid loss similar to frusemide at 10 mg kg-1 and all produced comparable BP reduction in combination with captopril (25-32 mm Hg). Triamterene did not increase fluid excretion and was ineffective. In SHR with bilateral ureteral ligation, the synergistic effect of frusemide was abolished while that of hydrochlorothiazide still occurred with a delayed onset. It is concluded that concomitant measurement of BP and urinary excretion in conscious, freely-moving SHR is a useful technique for studying new antihypertensive drugs. Using this preparation it was found that enhancement of the acute hypotensive response to captopril with concomitant diuretic therapy occurs within 10 min and is primarily related to the fluid and Na loss, regardless of the diuretic agent used.

Chronic antihypertensive treatment with captopril plus hydrochlorothiazide improves aortic distensibility in the spontaneously hypertensive rat

“…Hydrochlorothiazide and captopril are synergistic in SHR in which urinary loss is prevented by bilateral ureteral ligation (Chiu et al, 1985), although this has been contested (Chan et al, 1982). One argument in favour of an effect on vascular function and structure in our experiment can be based on the fact that the synergism between the two drugs was seen after 1 month of treatment only.…”

Effects of furosemide and the combination of furosemide and the labeled dosage of pimobendan on the circulating renin-angiotensin-aldosterone system in clinically normal dogs

“…The blood pressure-lowering properties of loop diuretics are typically attributed to loss of fluid and sodium, although these effects have been determined in rats and human patients parenterally administered loop diuretics regardless of volume status, which suggests the possibility of a direct vasodilatory mechanism. [22][23][24] This decrease in blood pressure is typically modest and is mediated and modified by the degree of sodium depletion as well as renin, angiotensin II, and prostaglandin concentrations. [22][23][24] The initial mild decrease in blood pressure in dogs that received furosemide alone may have been attributable to a direct vascular effect of furosemide.…”

“…[22][23][24] This decrease in blood pressure is typically modest and is mediated and modified by the degree of sodium depletion as well as renin, angiotensin II, and prostaglandin concentrations. [22][23][24] The initial mild decrease in blood pressure in dogs that received furosemide alone may have been attributable to a direct vascular effect of furosemide. 22 However, blood pressure did not change significantly in the dogs that received the combination of furosemide and pimobendan, despite suspected but unproven volume depletion and a possible furosemide-induced decrease in systemic vascular resistance.…”

Effects of combination of low doses of angiotensin-converting enzyme inhibitor and diuretics on renal function in spontaneously hypertensive rats: comparison between acute and chronic treatment

“…GFR and RBF in rats chronically treated with S5590 were not different from those of untreated GFR (ml/min/g kidney) SHR, despite a decreased amount of water (attested by decreased body weight and increased haematocrit) which might be related to the diuretic effect of indapamide.Thus, it is possible that the decreased RBF, secondary to the diuretic action of indapamide, was compensated by the marked vasodilatation induced by the indapamideperindopril combination and resulted in no significant change in filtration fraction. [17][18][19][20][21] This might explain why filtration fraction was not decreased although a reduction could have been expected, based on previous data obtained with ACE-I. 4,11,13,14 Given the fact that chronic treatment with S5590 induced a marked decrease in arterial pressure, it is important to note that glomerular filtration can be maintained only in a context in which efferent arteriolar vasodilation is more marked than afferent arteriolar vasodilatation.…”