Different antihypertensive effects of nifedipine in conscious experimental hypertensive and normotensive rats

Ishii, Hisakazu; Itoh, Keizo; Nose, Takashi

doi:10.1016/0014-2999(80)90365-9

Cited by 80 publications

(27 citation statements)

References 17 publications

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“…With nifedipine administration to nonpregnant rats, blood pressure decreased and, after 4 days of treatment, reached values similar to those in control pregnant rats. This is in agreement with the work of Ishii et al (8), who showed that nifedipine reduced the blood pressure of male normotensive rats by 21.8%, a level similar to that observed in the present study. In opposition, another study (14) reported that nifedipine failed to decrease blood pressure in male Sprague-Dawley rats.…”

Section: Discussionsupporting

confidence: 94%

Calcium channels contribute to the decrease in blood pressure of pregnant rats

Simaan

Cadorette

Poterek

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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Simaan, May, Chanterelle Cadorette, Matthieu Poterek, Jean St-Louis, and Michè le Brochu. Calcium channels contribute to the decrease in blood pressure of pregnant rats. Am J Physiol Heart Circ Physiol 282: H665-H671, 2002; 10.1152/ajpheart.01183.2001.-Pregnancy is associated with hemodynamic changes such as reduced vascular resistance and blood pressure. We reported that, during late pregnancy, the activity of voltage-dependent calcium channels (VDCC) is altered in the adrenal cortex and vascular smooth muscle. These observations suggested that the late pregnancy-induced decrease in blood pressure is linked to diminished VDCC function. We attempted to prevent pregnancy-induced reduced blood pressure with a calcium channel activator (CGP 28392) in pregnant rats and to mimic it by administration of a calcium channel blocker (nifedipine) to nonpregnant rats. Treatment was given from the 15th day of gestation for 7 days. The systolic blood pressure of CGP 28392-treated pregnant rats rose transiently for 2 days and then declined toward values of nontreated pregnant controls, although remaining higher. However, nonpregnant rats maintained their high arterial pressure throughout CGP 28392 treatment. Nifedipine lowered the blood pressure in nonpregnant rats to values of nontreated term-pregnant controls. Both agents did not affect body weight, water or food intake, plasma renin activity, and plasma aldosterone or corticosterone levels. Nifedipine and CGP 28392 treatment of nonpregnant and pregnant animals, respectively, did not modify the response of aortic rings to KCl. These results show that VDCC activation caused hypertension, which modified the extent of the decrease in blood pressure at the end of pregnancy. vascular vessels; nifedipine; CGP 28392 APPROXIMATELY 7-10% OF ALL PREGNANCIES are complicated by hypertension that is believed to result from the suppression of normal physiological responses to pregnancy. This syndrome is the major cause of maternal and perinatal morbidity and mortality. Its physiopathology is far from being understood because of our scant knowledge of the hemodynamic mechanisms responsible for reduced vascular resistance and blood pressure in normal pregnancy. Despite numerous reports on cardiovascular regulation during pregnancy (15), further investigation is needed.Several mechanisms have been proposed for the decrease in blood pressure and vascular resistance as well as for the associated blunted effects of vasopressor agents observed during pregnancy: 1) augmented liberation of endogenous vasodilators [prostacyclin and nitric oxide (NO)]; 2) modifications of mechanical properties and/or tissue composition (ratio of smooth muscle to connective tissue or elastin to collagen), leading to increased elasticity of blood vessel walls; and 3) reduced excitation-response coupling for vasoactive substances (angiotensin II, vasopressin, and phenylephrine) (13, 25). Accumulating evidence suggests that the latter mechanism may be significantly involved.In earlier studies, we reported that, during l...

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Section: Discussionsupporting

confidence: 94%

Calcium channels contribute to the decrease in blood pressure of pregnant rats

Simaan

Cadorette

Poterek

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…administered nifedipine, as has been reported after oral or intravenous administration. 20 On the contrary, i.c.v. administered nifedipine induced a sustained bradycardia.…”

Section: Discussionmentioning

confidence: 99%

Opposite central cardiovascular effects of nifedipine and BAY k 8644 in anesthetized rats.

Laurent¹,

Girerd²,

Tsoukaris-Kupfer³

et al. 1987

Hypertension

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SUMMARY The central cardiovascular effects of the calcium channel blocker nifedipine and the calcium channel activator BAY k 8644 were studied in anesthetized and ventilated normotensive Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). Both drugs were administered in a 1.5-/U.1 volume into the lateral ventricle of the brain (i.c.v.) or into the cisterna magna (i.e.). The injection of vehicle alone (i.e. or i.c.v.) did not significantly change mean arterial pressure (MAP) or heart rate. Nifedipine (5 and 50 /ug/kg) and BAY k 8644 (5 and SO fig/kg) induced opposite effects on MAP when centrally injected. Nifedipine decreased MAP and induced a bradycardia (i.c.v.) or no change in heart rate (i.e.), and BAY k 8644 increased MAP without any significant change in heart rate (i.e. or i.c.v.). These effects were more marked with the highest dose of either drug. These effects seemed to be of central origin, since they were suppressed by gang!ionic blockade by hexamethonium (100 mg/kg i.v.), whereas after hexamethonium the hypotensive and the hypertensive responses to intravenously injected nifedipine and BAY k 8644, respectively, were preserved. Bilateral vagotomy suppressed the bradycardia induced by i.c.v. administered nifedipine. Previously i.c.v. administered nifedipine (5 /u.g/kg) antagonized the pressor response to BAY k 8644 (5 jug/kg i.c.v.). Changes in MAP and heart rate were significantly more marked in SHR than in WKY. These results indicate that a calcium channel inhibitor and a calcium channel activator can modulate in opposite fashion central mechanisms involved in blood pressure control. (Hypertension 9: 132-138. 1987) KEY WORDS • 1,4-dihydropyridine • calcium channel blocker • spontaneously hypertensive rats • central nervous system • BAY k 8644 C ALCIUM channel blockers produce an in vitro direct depression of myocardial contractility and sinus node automaticity as well as relaxation of isolated coronary and peripheral blood vessels 1 ' 2 by inhibiting calcium influx into the cells. 3 The direct effects of calcium channel blockers on cardiovascular function can be modifed by their effects on the autonomic nervous system. 4 Calcium channel blockers have been reported to act peripherally to decrease neurotransmitter release at the neuromuscular junction 5 -6 and to modulate carotid baroreceptor function.7 Some evidence suggests that calcium channel blockers influence the autonomic nervous system at the central level, thus altering cardiovascular function.

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“…According to the methods of Tufro-McReddie (17), Sprague Dawley pups were given hydralazine (n ϭ 5) at a s.c. dose of 10 mg/kg daily from birth to 7 d of age, and compared with control littermates receiving saline (n ϭ 5). This dose of hydralazine has been shown to reduce blood pressure significantly (18,19). At the end of the study period, rats were killed, kidneys were harvested, and PCNA -positive and apoptotic cells were identified as described below.…”

Section: Methodsmentioning

confidence: 99%

Angiotensin Converting Enzyme Inhibition Decreases Cell Turnover in the Neonatal Rat Heart

Choi

2002

Pediatric Research

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The renin angiotensin system plays an important role in growth and development. Exposure of the neonate to an ACE inhibitor increases mortality and results in growth retardation and abnormal development. We have demonstrated that ACE inhibition in the developing kidney increases apoptosis and decreases cell proliferation, which may account for renal growth impairment. To evaluate the role of endogenous angiotensin in cardiac development, the relationship between ACE inhibition, cell proliferation, apoptosis, several modulators of apoptosis (bcl-2, bcl-xl, and clusterin) was examined in the developing rat heart. Thirty-five newborn rat pups were treated with enalapril (30 mg/kg/d) or a vehicle (control group) for 7 d, and hearts were removed for rt-PCR and Western blotting of bcl-2, bcl-xl, and clusterin. An additional 10 rat pups were treated with hydralazine (10 mg/kg/d) or a vehicle, to serve as a hypotensive control. Cell proliferation was determined by PCNA immunostaining, and apoptosis was detected using the total TUNEL technique. Enalapril treatment resulted in a 24% mortality, reduced body weight, and decreased heart weight (p Ͻ 0.05). Enalapril decreased proliferating myocytes by 23%, and reduced proliferating cardiac interstitial cells by 8.1% (p Ͻ 0.05). Enalapril also decreased myocytes apoptosis by 60%, but the proportion of myocytes undergoing apoptosis was 10-fold less than that of proliferating cells. Cardiac bcl-2 mRNA, clusterin mRNA, bcl-2 protein, and bcl-xl protein content were not changed, but clusterin protein expression was decreased by enalapril treatment. Hydralazine did not alter cardiac cell proliferation or apoptosis. We conclude that ACE inhibition decreases cell turnover in the developing rat heart, which may contribute to cardiac growth impairment. The loss of myocytes may lead to greater myocyte hypertrophy and myocardial damage during later life. The renin angiotensin system (RAS) plays a role in the maintenance of systemic arterial pressure in the newborn, and provides a homeostatic response to hypovolemia (1). Davidson (1) demonstrated parallel increases in plasma renin activity in arterial ANG-II concentration occurred in the immediate minutes after delivery. Furthermore, the release of catecholamines may be stimulated by the production of ANG II, and the activation of the sympathoadrenal system at birth has been implicated in several adaptive processes and structural integrity (2).In newborn animals and human infants, the activity of the RAS increases at birth, which is important in regulating cellular growth and organ differentiation (1, 3). ANG-II, which is a final product of the RAS, has been reported to exert atrophic effect on cardiac myocytes in cultures (4) and in vivo (5). ANG-II may stimulate a growth response in cardiac tissue indirectly, by increased blood pressure and total peripheral vascular resistance, which develops in response to ANG-II receptor coupling in the vasculature (5). Alternatively, ANG-II may have a direct effect by coupling to its cardiac membrane...

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Different antihypertensive effects of nifedipine in conscious experimental hypertensive and normotensive rats

Cited by 80 publications

References 17 publications

Calcium channels contribute to the decrease in blood pressure of pregnant rats

Calcium channels contribute to the decrease in blood pressure of pregnant rats

Opposite central cardiovascular effects of nifedipine and BAY k 8644 in anesthetized rats.

Angiotensin Converting Enzyme Inhibition Decreases Cell Turnover in the Neonatal Rat Heart

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