Journal of Ethnopharmacology 73 (2000) 95 – 100

www.elsevier.com/locate/jethpharm

Acute diuretic, natriuretic and hypotensive effects of a

continuous perfusion of aqueous extract of Urtica dioica in
the rat
Abdelhafid Tahri *, Sabah Yamani, Abdelkhaleq Legssyer, Mohammed Aziz,
Hassane Mekhfi, Mohammed Bnouham, Abderrahim Ziyyat
Laboratoire de Physiologie et Pharmacologie Cellulaire, Faculté des Sciences, Uni6ersité Mohammed Premier, B.P. 524,
Oujda 60000, Morocco
Received 27 September 1999; received in revised form 4 May 2000; accepted 22 May 2000

Abstract

This study was performed on anaesthetized male Wistar rats that received a continuous intravenous perfusion
during 1.25 h of an aqueous extract of aerial parts of Urtica dioica L. (Urticaceae) at a low dose of 4 mg/kg/h or at
a high dose of 24 mg/kg/h, or furosemide (control diuretic) at a dose of 2 mg/kg/h. As compared with a control
period in each rat, the arterial blood pressure was reduced proportionally to the dose of the perfusion of the plant
extract (15 and 38%, PB 0.001, respectively). These effects were accompanied by a correlative increase of diuresis (11
and 84%, PB 0.001, respectively) and natriuresis (28 and 143%, PB 0.001, respectively). In the rats perfused by
furosemide, the arterial blood pressure was reduced by 28% (PB 0.001). The diuresis and natriuresis were also
increased proportionally in this case (85 and 155%, PB 0.001, respectively). Nevertheless, the hypotensive action of
U. dioica was reversible during the recovery periods in about 1 h with the lower dose of the plant extract and
furosemide, while the effect of the higher dose was persistent, indicating a possible toxic effect. In conclusion, the
results demonstrate an acute hypotensive action of U. dioica that indicates a direct effect on the cardiovascular
system. Moreover, diuretic and natriuretic effects were also observed, suggesting an action on the renal function.
Finally, the plant extract seems to have a toxic effect at the higher dose. © 2000 Elsevier Science Ireland Ltd. All
rights reserved.

Keywords: Urtica dioica; Urticaceae; Aqueous extract; Furosemide; Continuous perfusion; Hypotensive action; Diuretic effect;
Natriuretic effect; Toxic effect; Rat

1. Introduction

It is known in traditional therapy that Urtica

* Corresponding author.
E-mail address: atahri@sciences.univ-oujda.ac.ma (A. dioica L. (Urticaceae) or nettle has a hypotensive
Tahri). effect (Garnier et al., 1961). Therewith, some

0378-8741/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 3 7 8 - 8 7 4 1 ( 0 0 ) 0 0 2 7 0 - 1
96 A. Tahri et al. / Journal of Ethnopharmacology 73 (2000) 95–100
other actions of this plant were reported such as
anti-inflammatory effects (Obertreis et al., 1996;
Riehemann et al., 1999) and stimulation of prolif-
eration of human lymphocytes (Wagner et al.,
1989). The effects of the nettle are also evoked in
the therapy of the prostatic hyperplasia (Krzeski
et al., 1993; Hiramo et al., 1994; Lichius and
Muth, 1997), but this plant has no hypoglycemic
action, as reported by Raman-Ramos et al.
(1992), Swanston-Flatt et al. (1989). Moreover, it
has been shown in an inquiry realized by our
laboratory that U. dioica is frequently used in the
traditional therapy of hypertension in northeast-
ern Morocco (Ziyyat et al., 1997). Thus, the pur-
pose of the present experiments was to investigate
the pharmacological effects of a continuous perfu-
sion of aqueous extract of U. dioica on the arterial
blood pressure, and its possible correlation with
diuretic and natriuretic actions in anaesthetized
rats.
2. Materials and methods
2.1. Collection of the plant and preparation of
aqueous extract
The aerial parts of U. dioica were collected in
northeastern Morocco in the proximity of Oujda
city. They were then dried and sliced. Afterwards,
10 g of small pieces of the aerial parts of the plant
were infused into 100 ml boiled distilled water
during 20 min. After decantation and filtration,
the filtrate was again dried in an incubator at a
temperature of 50°C. The aqueous extract was
then prepared at different concentrations in iso-
tonic physiological solution (0.9% NaCl).
Fig. 1. Representation of the experimental protocol. Eq, equlibration; C1, C2, control periods; E1, E2, experimental periods; R1,
R2, recovery periods.
2.2. Preparation of animals
Male Wistar rats (250–300 g) were fasted
overnight but had free access to tap water. On the
day of the experimentation, they were anaes-
thetized by an intraperitoneal injection of ure-
thane (2 g/kg body weight). After anaesthesia,
they were placed on a heated table to maintain
their body temperature at around 37°C. A tra-
cheotomy was performed in order to facilitate the
respiration. A catheter was then placed into the
right external jugular vein for subsequent perfu-
sion of solutions. Each femoral artery was
catheterized in order to collect blood samples, and
to directly and continuously measure the arterial
blood pressure, using a mercurial manometer. The
bladder was then cannulated in order to collect
urine samples.
2.3. Experimental protocol and perfusions
After the surgical preparation, a solution of
2.5% bovine serum albumin prepared into a phys-
iological liquid containing 0.9% NaCl was per-
fused intravenously at a rate of 150 ml/min for 5
min followed by 70 ml/min for 30 min. The perfu-
sion of this solution is used in order to maintain a
correct plasmatic oncotic pressure and to avoid
fluid shifts during surgery (Maddox et al., 1977).
After this perfusion period, a physiological solu-
tion (0.9% NaCl) used as vehicle was continuously
perfused at a rate of 45 ml/min. After an equilibra-
tion period (Eq) during 15 min, two control mea-
surement periods (C1 and C2) of 30 min each
were started (Fig. 1). At the end of these periods,
this perfusion was discontinued and replaced by a
solution of aqueous extract of U. dioica. Two
different concentrations of the plant extract were
 A. Tahri et al. / Journal of Ethnopharmacology 73 (2000) 95–100 97

Table 1
Effects of the perfusion of an aqueous extract of U. dioica or furosemide on ABP and Hct in the anaesthetized rata

Parameter Treatment C1 C2 E1 E2 R1 R2

ABP (mmHg) Plant extract

4 mg/kg/h (n= 6) 114 91 114 91 103 91* 97 9 1* 104 9 1* 112 92
24 mg/kg/h (n=6) 1149 1 114 91 8591* 71 9 1* 77 92* 80 91*
Furosemide
2 mg/kg/h (n= 4) 112 9 1 112 91 90 91* 81 9 1* 94 91* 112 91
Hct (%) Plant extract
4 mg/kg/h (n=6) 5290.3 52 90.5 52 9 0.5 52 9 0.2 52 90.2 52 9 0.2
24 mg/kg/h (n= 6) 549 0.1 54 9 0.1 4790.2* 47 90.2* 49 9 0.2* 50 9 0.1*
Furosemide
2 mg/kg/h (n= 4) 549 0.2 54 9 0.2 4890.2* 48 90.1* 49 9 0.1* 53 9 0.2*

Mean values 9S.E.M. are presented. C1, C2, control periods; E1, E2, experimental periods; R1, R2, recovery periods. *
a

PB0.001 versus control periods (ANOVA followed by Bonferroni t-test).

used (4 and 24 mg/kg/h). In other experiments, a
solution of the pharmacological diuretic,
furosemide, prepared into vehicle solution, was
perfused at a rate of 2 mg/kg/h in order to
compare its effects with those of the plant extract.
After an equilibration period during 15 min, two
experimental measurement periods (E1 and E2) of
30 min each were undertaken. In each period
described, the arterial blood pressure was continu-
ously measured. Therewith, the urine was contin-
uously collected and weighed, and small blood
samples were taken at the midpoint of the periods
in order to determine the haematocrit. Finally, the
perfusion of the plant extract was discontinued
and replaced again by vehicle solution. After an
equilibration period of 15 min, two recovery mea-
surement periods (R1 and R2) of 30 min each
were started. During these periods, the arterial
blood pressure as well as the haematocrit were
measured.
2.4. Analytical methods and calculations
Arterial blood pressure was directly and contin-
uously measured from a femoral artery catheter.
Hematocrit was determined by the ratio of plasma
volume/blood volume, using a specific table.
Urine volume was determined from urine weight.
The diuresis was calculated as the ratio of urine
volume/time period. The urinary sodium concen-
tration was measured with a flame photometer.
The natriuresis was then calculated as the product
of urinary sodium concentration and diuresis. The
results of diuresis and natriuresis of each pair of
measurement periods (C1–C2 and E1–E2) were
averaged so that the mean values represent, re-
spectively, a control period (C) or an experimental
period (E).
2.5. Statistical analysis
Results are expressed as means9 S.E.M.
Within-group comparisons were performed by
analysis of variance (ANOVA) test for repeated
measurements followed by the Bonferroni t-test
(Wallenstein et al., 1980). Therewith, the paired
t-test was used where appropriate. In all analyses,
PB 0.05 was considered significant.
3. Results
3.1. Effects on the arterial blood pressure
The results of arterial blood pressure (ABP)
and haematocrit (Hct) are presented in Table 1.
Moreover, the time course of ABP is showed in
Fig. 2. In the first group (n=6), during the con-
trol periods (C1 and C2), where the vehicle solu-
tion (0.9% NaCl) was perfused, ABP was stable
and then decreased progressively and significantly
following the perfusion of U. dioica extract at the
dose of 4 mg/kg/h (maximum reduction, 15%;
ANOVA, PB0.001). After the return to the per-
98 A. Tahri et al. / Journal of Ethnopharmacology 73 (2000) 95–100

fusion of vehicle during the recovery periods,
ABP increased progressively so that it reached a
similar value to the control periods in the second
30-min period (R2). Therewith, Hct remained sta-
ble during the experience. In the second group
(n = 6), ABP was stable during the control periods
and decreased progressively and significantly fol-
lowing the perfusion of U. dioica extract at the
dose of 24 mg/kg/h (maximum reduction, 38%;
ANOVA, P B0.001). During the recovery peri-
ods, ABP then increased slowly so that the re-
versibility was not complete since the value
reached remained 30% lower (ANOVA, P B
0.001) as compared with the control periods.
Moreover, Hct decreased during the perfusion of
the plant extract (maximum reduction, 13%;
ANOVA, PB0.001) and increased during the
recovery periods, but the value of the period R2
remained 7% lower (ANOVA, P B 0.001) than
that of the control periods. In the third group
(n = 4), ABP was stable during the control periods
and then decreased progressively and significantly
following the perfusion of furosemide at a dose of
2 mg/kg/h (maximum reduction, 28%; ANOVA,
PB 0.001). During the recovery periods, ABP
then increased progressively so that it returned to
a similar value to the control periods in the
second 30-min period (R2). Therewith, Hct de-
creased during the perfusion of furosemide (maxi-
mum decrease, 11%; ANOVA, P B 0.001) and
returned progressively during the recovery periods
to a similar value of the control periods.
3.2. Effects on the diuresis and natriuresis
The results of diuresis (UV) and natriuresis
(UNaV) are shown in Table 2. In the first group
(n= 6), UV and UNaV increased moderately but
significantly following the perfusion of U. dioica
extract at the dose of 4 mg/kg/h (11 and 28%,
respectively; paired t-test, PB 0.001). Therewith,
in the second group (n= 6), UV and UNaV in-
creased significantly following the perfusion of U.
dioica extract at the dose of 24 mg/kg/h (84 and
143%, respectively; paired t-test, PB0.001). Fur-
thermore, in the third group (n= 4), UV and

Fig. 2. Time evolution of arterial blood pressure before and following continuous perfusion of an aqueous extract of U. dioica or
furosemide in the rat. C1, C2, control periods; E1, E2, experimental periods; R1, R2, recovery periods. Mean values9 S.E.M. are
presented. * PB 0.001 versus control periods (ANOVA followed by Bonferroni t-test).
 A. Tahri et al. / Journal of Ethnopharmacology 73 (2000) 95–100 99

Table 2 the heart rate following a perfusion of the plant

Effects of the perfusion of an aqueous extract of U. dioica or
extract. Thus, the diuretic and natriuretic effects
furosemide on diuresis (UV) and natriuresis (UNaV) in the
anaesthetized rata of the plant extract observed in the present study
could participate in a chronic hypotensive action,
Parameter Treatment C E but the acute action was not explained since the
reduction of haematocrit observed with the higher
UV (ml/min) Plant extract
dose of the plant extract and furosemide indicates
4 mg/kg/h 11.0 9 0.2 12.29 0.2*
(n =6)
an augmentation of the circulating plasma vol-
24 mg/kg/h 10.8 9 0.1 19.99 0.1* ume. Nevertheless, the investigation of the
(n= 6) glomerular filtration rate as well as renal blood
Furosemide flow will be interesting to determine the part of
2 mg/kg/h 11.39 0.4 20.9 9 0.2*
renal glomerular and tubular effects of the plant
(n =4)
UNaV Plant extract
extract. Therewith, these diuretic and natriuretic
(mEq/min) effects could not be attributed to a sodium sur-
4 mg/kg/h 0.71 9 0.01 0.919 0.01* charge since the solution of the extract of U.
(n= 6) dioica contains a negligible quantity of this elec-
24 mg/kg/h 0.70 90.01 1.709 0.10*
trolyte. Furthermore, the reversibility of the arte-
(n =6)
Furosemide rial blood pressure decrease was complete with
2 mg/kg/h 0.73 90.01 1.869 0.03* the lower dose of U. dioica as well as furosemide
(n =4) in about 1 h, while the hypotensive effect of the
higher dose persisted. This suggests that the active
a
Mean values 9S.E.M. are presented. C, control period; E, components that may be contained by the plant
experimental period. * PB0.001 versus control period (paired
t-test).
extract could act on some systems with a mode of
action slowly reversible or it could have a toxic
UNaV increased significantly following the perfu- effect at the higher dose. Finally, some substances
sion of furosemide at a dose of 2 mg/kg/h (85 and such as acetylcholine, histamine, formic acid, tan-
155%, respectively; paired t-test, P B 0.001). nins and other possible vasoactive products are
related among the contents of U. dioica (Garnier
et al., 1961; Smallman and Maneckjee, 1981; Stu-
art, 1981; Sijelmassi, 1993). Nonetheless, recent
4. Discussion results of our laboratory (not shown) indicate a
persistent hypotensive action of the extract of U.
The results of the present study demonstrate a dioica in the presence of a muscarinic receptor
progressive reduction of the arterial blood pres- antagonist, atropin, so that the possible incrimi-
sure following a continuous intravenous perfusion nation of acetylcholine will be discarded.
of aqueous extract of U. dioica that depended on In conclusion, the results demonstrate an acute
the dose perfused. At the same time, both diuresis hypotensive action of aqueous extract of U. dioica
and natriuresis increased proportionally to the that indicates a direct effect on the cardiovascular
dose perfused. Furthermore, the perfusion of system. Moreover, diuretic and natriuretic effects
furosemide, used as a control pharmacological were also observed, suggesting an action on the
diuretic, at a dose of 2 mg/kg/h produced a renal function. Finally, the plant extract seems to
reduction of the arterial blood pressure, which have a toxic effect at the higher dose.
was also accompanied by increases in both diure-
sis and natriuresis. The observed acute hypoten- Acknowledgements
sive effect of the plant extract indicates a direct
action of its components on the cardiovascular The authors are grateful to the National Fund
system. In this way, results obtained in our labo- of Scientific Research of Morocco (FNRS) for
ratory (not shown) demonstrated a reduction in financial support.
100 A. Tahri et al. / Journal of Ethnopharmacology 73 (2000) 95–100
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