The acute renal haemodynamic and endocrine response to felodipine in normal man

Jenkins, David; Craig, Kate; Cumming, Allan D.; Watson, M.

doi:10.1007/bf00542491

“…Rather, the fact that mibefradil increases sodium excretion without changing GFR argues against a pivotal role for GFR in mediating calcium channel antagonistinduced natriuresis. The latter observations are consistent with previous reports that calcium channel antagonists augment natriuresis even when RPF and GFR are unchanged [8,28], and further suggest that an important site of action in mediating the calcium channel antagonistinduced natriuresis is the renal tubule. Indeed, the present study demonstrates that both efonidipine and mibefradil caused marked increases in FE Na (102p44 % and 67p20 % respectively).…”

Section: Discussionsupporting

confidence: 90%

“…For example, Seino et al [39] reported that pretreatment with indomethacin failed to affect diltiazem-induced natriuresis in anaesthetized rabbits. Furthermore, Jenkins et al [28] examined the natriuretic action of calcium channel antagonists in normal humans, and compared the effects of these antagonists with that during blockade of PGs. They observed the same degree of natriuresis even though urinary PG excretion was inhibited by indomethacin.…”

Section: Discussionmentioning

confidence: 98%

Divergent natriuretic action of calcium channel antagonists in mongrel dogs: renal haemodynamics as a determinant of natriuresis

Honda¹,

Hayashi²,

MATSUDA³

et al. 2001

View full text Add to dashboard Cite

This study examined the effects of different types of calcium channel antagonists on renal haemodynamics and natriuresis. The intravenous infusion of nifedipine (L-type blocker), efonidipine (L/T-type blocker) or mibefradil (predominant T-type blocker) into anaesthetized dogs elicited similar, albeit modest, reductions in blood pressure. Nifedipine (1 microgram.min(-1).kg(-1)) increased renal plasma flow (RPF) (23+/-6%; P<0.05) and glomerular filtration rate (GFR) (25+/-5%; P<0.05) (all values are means+/-S.E.M., n=7). Efonidipine (0.33 microgram .min(-1).kg(-1)) also elevated RPF (18+/-6%; P<0.05), and tended to increase GFR (17+/-8%; P=0.08). These antagonists exerted contrasting actions on the filtration fraction (FF), with an increase being elicited by nifedipine, whereas efonidipine had no effect. Furthermore, mibefradil (0.01-1 microgram.min(-1).kg(-1)) slightly elevated RPF (between 5+/-3% and 8+/-3%), but failed to alter GFR, resulting in a decrease in FF. Nifedipine slightly increased urinary sodium excretion (U(Na)V) (29+/-16% increase at 1 microgram .min(-1).kg(-1)) and fractional sodium excretion (FE(Na)) (18+/-14%), whereas efonidipine (0.33 microgram .min(-1).kg(-1)) elicited marked elevations in U(Na)V (110+/-38%; P<0.05) and FE(Na) (102+/-44%; P<0.05). Mibefradil (1 microgram .min(-1).kg(-1)) exerted a moderate natriuretic action [U(Na)V, +60+/-32% (P=0.1); FE(Na), +67+/-20% (P<0.05)]. Furthermore, although a positive correlation was observed between U(Na)V and urinary nitrate/nitrite excretion, no differences were noted between the various calcium channel antagonists. Collectively, this study demonstrates that the glomerular haemodynamic and natriuretic actions of these calcium channel antagonists, which possess diverse blocking activities on L/T-type channels, vary. Based on the divergent actions on FF (i.e. increase, no change and decrease by nifedipine, efonidipine and mibefradil respectively), the natriuretic action of calcium channel antagonists is possibly attributed to the inhibition of tubular sodium reabsorption associated with increased post-glomerular blood flow, rather than increased GFR.

show abstract

“…The latter observations are consistent with previous reports that calcium channel antagonists augment natriuresis even when RPF and GFR are unchanged [8,28], and further suggest that an important site of action in mediating the calcium channel antagonistinduced natriuresis is the renal tubule. In the present study, we have demonstrated that nifedipine and efonidipine elevate GFR.…”

Section: Discussionsupporting

confidence: 92%

Divergent natriuretic action of calcium channel antagonists in mongrel dogs: renal haemodynamics as a determinant of natriuresis

Honda

¹

,

Hayashi

²

,

Matsuda

³

et al. 2001

View full text Add to dashboard Cite

This study examined the effects of different types of calcium channel antagonists on renal haemodynamics and natriuresis. The intravenous infusion of nifedipine (L-type blocker), efonidipine (L/T-type blocker) or mibefradil (predominant T-type blocker) into anaesthetized dogs elicited similar, albeit modest, reductions in blood pressure. Nifedipine (1 microgram.min(-1).kg(-1)) increased renal plasma flow (RPF) (23+/-6%; P<0.05) and glomerular filtration rate (GFR) (25+/-5%; P<0.05) (all values are means+/-S.E.M., n=7). Efonidipine (0.33 microgram .min(-1).kg(-1)) also elevated RPF (18+/-6%; P<0.05), and tended to increase GFR (17+/-8%; P=0.08). These antagonists exerted contrasting actions on the filtration fraction (FF), with an increase being elicited by nifedipine, whereas efonidipine had no effect. Furthermore, mibefradil (0.01-1 microgram.min(-1).kg(-1)) slightly elevated RPF (between 5+/-3% and 8+/-3%), but failed to alter GFR, resulting in a decrease in FF. Nifedipine slightly increased urinary sodium excretion (U(Na)V) (29+/-16% increase at 1 microgram .min(-1).kg(-1)) and fractional sodium excretion (FE(Na)) (18+/-14%), whereas efonidipine (0.33 microgram .min(-1).kg(-1)) elicited marked elevations in U(Na)V (110+/-38%; P<0.05) and FE(Na) (102+/-44%; P<0.05). Mibefradil (1 microgram .min(-1).kg(-1)) exerted a moderate natriuretic action [U(Na)V, +60+/-32% (P=0.1); FE(Na), +67+/-20% (P<0.05)]. Furthermore, although a positive correlation was observed between U(Na)V and urinary nitrate/nitrite excretion, no differences were noted between the various calcium channel antagonists. Collectively, this study demonstrates that the glomerular haemodynamic and natriuretic actions of these calcium channel antagonists, which possess diverse blocking activities on L/T-type channels, vary. Based on the divergent actions on FF (i.e. increase, no change and decrease by nifedipine, efonidipine and mibefradil respectively), the natriuretic action of calcium channel antagonists is possibly attributed to the inhibition of tubular sodium reabsorption associated with increased post-glomerular blood flow, rather than increased GFR.

show abstract

“…Acute and long-term effects of felodipine on renal functions have been investigated by several authors. Renal blood flow and glomerular filtra tion rate (GFR) have been reported to be unchanged by Ek et al [11], DiBona et al [ 10], Binetti et al [17], Jenkins et al [ 18] and Schmitz et al [5], while others observed an increase in renal flow and ERPF by felodipine [8,19], Herlitz et al [19] have reported an increase in GFR and only a slight increase in renal plasma flow during long term treatment of felodipine. They have concluded that felodipine has a relaxation effect on the afferent arteriole leading to an enhanced GFR.…”

Section: Discussionmentioning

confidence: 96%

Scintigraphic Evaluation of the Short- and Long-Term Renal Effects of Oral Felodipine Using Technetium-99m-Mercaptoacetyl Triglycine

Özdemir¹,

Erbaş

²

,

Uğur

³

et al. 1993

Am J Nephrol

3

0

View full text Add to dashboard Cite

The short- and long-term effect of felodipine on renal perfusion and tubular function was investigated using a new renal tubular imaging agent, ^99mTc-mercaptoacetyl triglycine (^99mTc-MAG3). Twelve patients with essential hypertension (mean age = 49 + 8 years) were studied. Renal scintigraphies with 180 MBq ^99mTc-MAG3 were performed at baseline, at the 2nd hour following oral administration of 5 mg felodipine and 4 weeks later on 5-10 mg daily felodipine therapy. The time-activity curves of each kidney were obtained following background subtraction. The ^99mTc-MAG3 clearance value was measured for each kidney. In addition, perfusion index (PI), reno index, time to maximum, half-maximum and two thirds of maximum activity values of each kidney were calculated. Systolic and diastolic blood pressures were significantly lowered with long-term administration of felodipine (from 159 ± 12/105 ± 5 to 141 ± 11/87 ± 7 mm Hg, p = 0.01 and p = 0.002, respectively). Heart rate did not change significantly. Initially, a decrease in PI indicating an increase in renal blood flow (from 246 ± 96 to 194 ± 54, p= 0.01) was observed, whereas no change was noted during the chronic administration (to 230 ± 69, p = NS). Total clearance of ^99mTc-MAG3 was decreased nonsignificantly following the initial dose of felodipine (from 361 ± 93 to 351 ± 91 ml/ min, p = NS). During long-term therapy, felodipine did not alter the perfusion and tubular function of the kidneys. Our results indicated that felodipine causes a significant increase in renal blood flow initially, even with a nonsignificant change in systemic blood pressure.

show abstract

The acute renal haemodynamic and endocrine response to felodipine in normal man

Cited by 8 publications

References 25 publications

Divergent natriuretic action of calcium channel antagonists in mongrel dogs: renal haemodynamics as a determinant of natriuresis

Divergent natriuretic action of calcium channel antagonists in mongrel dogs: renal haemodynamics as a determinant of natriuresis

Divergent natriuretic action of calcium channel antagonists in mongrel dogs: renal haemodynamics as a determinant of natriuresis

Scintigraphic Evaluation of the Short- and Long-Term Renal Effects of Oral Felodipine Using Technetium-99m-Mercaptoacetyl Triglycine

Contact Info

Product

Resources

About