Methyl Ester-induced Hypertension Research Articles

Daily consumption of wild olive (acebuche) oil reduces blood pressure and ameliorates endothelial dysfunction and vascular remodelling in rats with NG-nitro-L-arginine methyl ester-induced hypertension.

Despite numerous reports on the beneficial effects of olive oil in the cardiovascular context, very little is known about the olive tree's wild counterpart (Olea europaea, L. var. sylvestris), commonly known as acebuche (ACE) in Spain. The aim of this study was to analyse the possible beneficial effects of an extra virgin ACE oil on vascular function in a rodent model of arterial hypertension (AH) induced by NG-nitro-l-arginine methyl ester (L-NAME). Four experimental groups of male Wistar rats were studied: (1) normotensive rats (Control group); (2) normotensive rats fed a commercial diet supplemented with 15 % (w/w) ACE oil (Acebuche group); (3) rats made hypertensive following administration of L-NAME(L-NAME group); and (4) rats treated with L-NAME and simultaneously supplemented with 15 % ACE oil (LN + ACE group). All treatments were maintained for 12 weeks. Besides a significant blood pressure (BP)-lowering effect, the ACE oil-enriched diet counteracted the alterations found in aortas from hypertensive rats in terms of morphology and responsiveness to vasoactive mediators. In addition, a decrease in hypertension-related fibrotic and oxidative stress processes was observed in L-NAME-treated rats subjected to ACE oil supplement. Therefore, using a model of AH via nitric oxide depletion, here we demonstrate the beneficial effects of a wild olive oil based upon its vasodilator, antihypertensive, antioxidant, antihypertrophic and antifibrotic properties. We postulate that regular inclusion of ACE oil in the diet can alleviate the vascular remodelling and endothelial dysfunction processes typically found in AH, thus resulting in a significant reduction of BP.

Zinc complexation improves angiotensin II receptor type 1 blockade and in vivo antihypertensive activity of telmisartan.

Background: Angiotensin II receptor blockers were designed as therapeutic agentsto block the binding site of the angiotensin II receptor type 1 (AT1R). Methodology: The structure of telmisartan was modified by coordination to the biometal Zn(II), resulting in the compoundZnTelm. Its antihypertensive activity and cellular mechanisms in comparison to telmisartan were studied. Results:Compared with telmisartan, ZnTelm displayed stronger binding to AT1R (binding studies on AT1R-transfectedhuman embryonic kidneycells) and a greater reduction of reactive oxygen species and cytosolic calcium concentration induced by angiotensinII. The antihypertensive activity of the complex (assessed in an N(G)-Nitro-L-arginine methyl ester-induced hypertension model) was significantly higher. ZnTelm also reduced hypertrophy in aortic artery rings and tubular collagen deposition. Conclusion: ZnTelm enhances the AT1R blockade and consequently its antihypertensive effect.

Renoprotective Effects of Antroquinonol in Rats with Nω-Nitro-l-Arginine Methyl Ester-Induced Hypertension.

Endothelial dysfunction leads to elevation of blood pressure and vascular remodeling, which may result in tissue injuries. The aim of this study was to investigate the mechanisms and effects of antroquinonol on hypertension and related renal injuries. Rats were fed water containing 25 mg/kg/day Nω-nitro-l-arginine methyl ester (L-NAME) to induce hypertension, and a diet with or without antroquinonol (20 or 40 mg/kg/day) for a 9-week experiment. During the experimental period, antroquinonol reduced the elevation of systolic and diastolic blood pressure. At the end of the study, we found that the antroquinonol groups had lower serum creatinine, renal endothelin-1, angiotensin II, and malondialdehyde levels and arteriole thickening. We found that the 40 mg/kg/day antroquinonol group had lower renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activities, greater nuclear factor erythroid-2, and heme oxygenase-1 expressions. Moreover, we also found that antroquinonol decreased proinflammatory cytokine concentrations in the kidney by modulating the nuclear factor-κB pathway. These results suggest that antroquinonol may ameliorate hypertension and improve renal function by reducing oxidative stress and inflammation in rats with endothelial dysfunction.

Correction: Antihypertensive Effect of Polyphenol-Rich Fraction of Azadirachta indica on Nω-Nitro-L-Arginine Methyl Ester-Induced Hypertension and Cardiorenal Dysfunction.

Azadirachta indica (AI) is a medicinal plant with reported antioxidant and cardio-protective properties. The use of plant-based polyphenols has become greatly increased in the last one decade. The present study investigated the protective effect of the polyphenol-rich fraction (PRF) of the methanol-extract of Azadirachta indica against Nω-Nitro-L-Arginine Methyl Ester (L-NAME) induced hypertension and cardiorenal dysfunction in rats. Fifty (50) Wistar albino rats were grouped into five groups. Group A, the control, was administered potable water. Groups B-E received orally, 40 mg/kg of L-NAME only, 40 mg/kg of L-NAME and 100 mg/kg of AI extract, 40 mg/kg of L-NAME and 200 mg/kg of AI extract, and 40 mg/kg of L-NAME and 25 mg/kg of captopril, respectively for 21 days. The results of the present study revealed that L-NAME administration led to a significant increase in systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. Markers of oxidative stress (malondialdehyde,protein carbonyl) increased significantly while there was reduction in reduced glutathione level, activities of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase as well nitric oxide bioavailability. Immunohistochemistry revealed higher expressions of nuclear factor kappa beta (NF-kB) and kidney injury molecule 1(Kim-1) and lower expressions of nuclear factor erythroid 2–related factor 2 (Nrf2) in hypertensive rats. Our results indicated that with PRF of AI restored high blood pressure, reduced markers of oxidative stress, normalized serum NO bioavailability and increased the expressions of Nrf2. Hence, PRF of Azadirachta indica could be used for the treatment of hypertension.

Acute toxicity study and prevention of Nω-nitro-L-arginine methyl ester-induced hypertension by <i>Osteopermum imbricatum</i>

Purpose: To determine the phytochemical content, toxicity and hypertension prevention effects of Osteospermum imbricatum leaf and root extracts.Methods: Phytochemical screening of leaf and root extracts of O. imbricatum was performed by colorimetric procedure. Acute toxicity of leaf and root extracts was conducted in two phases; phase I consisted of three groups of mice (n = 3) for each dose level of 10, 100 and 1000 mg/kg while phase II had three mice that received 1600, 2900 or 5000 mg/kg. Wistar rats were grouped into 7 groups that were co-treated with L-NAME and normal saline or L-NAME and hydroethanolic leaf extract (150 and 300 mg/kg) or L-NAME and hydroethanolic root extract (150 and 300 mg/kg) or L-NAME and amlodipine (5 mg/kg) or normal saline only for 4 weeks. Treatment was carried out via the oral route while blood pressure was measured weekly for 4 weeks by non-invasive tail cuff method.Results: The phytochemical profile of the leaf and root extracts revealed the presence of phenols, terpenoids, flavonoids, glycosides, tannins, steroids and saponins. Both the leaf and root extracts were toxic at 5000 mg/kg with an LD50 of 3807.89 mg/kg. In the fourth week of the study, only the leaf extract significantly (p < 0.01) prevented the progression of L-NAME induced hypertension; systolic and diastolic blood pressure of the group treated with L-NAME and leaf extract (300 mg/kg) were 183 ± 1 and 140 ± 1 mmHg, respectively, compared to the group that was treated with L-NAME and normal saline which produced systolic and diastolic BP values of 213 ± 3 and 172 ± 4 mmHg, respectively. The extracts, especially OIR300, exhibited diuretic effects in the second and third week of study by promoting excretion of 16 and 19 ml urine, respectively, compared to 11 and 14 ml for LN group.Conclusion: The results suggest that O. imbricatum is moderately toxic at a high dose and contains a wide range of phytochemicals which offer partial protection against the development of nitric oxide deficiency hypertension.Keywords: Hypertension, Phytochemicals, Acute toxicity, Nω-Nitro-L-arginine methyl ester (L-NAME), Osteospermum imbricatum

Antihypertensive Effect of Polyphenol-Rich Fraction of Azadirachta indica on Nω-Nitro-L-Arginine Methyl Ester-Induced Hypertension and Cardiorenal Dysfunction.

Azadirachta indica (AI) is a medicinal plant with reported antioxidant and cardio-protective properties. The use of plant-based polyphenols has become greatly increased in the last one decade. The present study investigated the protective effect of the polyphenol-rich fraction (PRF) of the methanol-extract of Azadirachta indica against Nω-Nitro-L-Arginine Methyl Ester (L-NAME) induced hypertension and cardiorenal dysfunction in rats. Fifty (50) Wistar albino rats were grouped into five groups. Group A, the control, was administered potable water. Groups B-E received orally, 40 mg/kg of L-NAME only, 40 mg/kg of L-NAME and 100 mg/kg of AI extract, 40 mg/kg of L-NAME and 200 mg/kg of AI extract, and 40 mg/kg of L-NAME and 25 mg/kg of captopril, respectively for 21 days. The results of the present study revealed that L-NAME administration led to a significant increase in systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. Markers of oxidative stress (malondialdehyde,protein carbonyl) increased significantly while there was reduction in reduced glutathione level, activities of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase as well nitric oxide bioavailability. Immunohistochemistry revealed higher expressions of nuclear factor kappa beta (NF-kB) and kidney injury molecule 1(Kim-1) and lower expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) in hypertensive rats. Our results indicated that with PRF of AI restored high blood pressure, reduced markers of oxidative stress, normalized serum NO bioavailability and increased the expressions of Nrf2. Hence, PRF of Azadirachta indica could be used for the treatment of hypertension.

Effects of oligomeric grape seed proanthocyanidins on L-NAME-induced hypertension in pregnant mice: Role of oxidative stress and endothelial dysfunction.

The aim of this study was to investigate the effects of Grape Seed Proanthocyanidins (GSP) on Nω-Nitro-L-arginine methyl ester-induced hypertension in pregnant mice. Fifty Kunming mice were randomized into control, control+GSP, model, and model+GSP. Three weeks later, the artery systolic blood pressure was examined and the related pathological changes were detected. Aorta relaxation function was assessed by aorta ring apparatus. Blood urea nitrogen and serum creatinine were measured by an automatic biochemistry analyzer. Colorimetric analysis, enzyme-linked immunosorbent assay, immunofluorescence, and western blot were applied to detect related indicator in serum, cardiac, and kidney tissues. The results showed that GSP treatment for 3weeks could improve cardiovascular and kidney remodeling indexes and decrease blood urea nitrogen and serum creatinine content in serum, as well as could ameliorate oxidative stress status and endothelial dysfunction. Therefore, it is for the first time found that GSP exerts protective effect against Nω-Nitro-L-arginine methyl ester-induced hypertension in pregnant mice, which provided a theoretical basis for potential application in the clinic.

Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with NG-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2.

Gallic acid, a natural chemical found in plants, has been reported to show antioxidant, anticancer, and anti-inflammatory effects. We investigated the efficacy of a short-term or long-term treatment with gallic acid in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive mice and the underlying regulatory mechanism. Hypertension was sufficiently induced after 2 weeks of L-NAME administration. Cardiac remodeling was assessed by echocardiography. Hypertrophic markers, transcription factors, and fibrosis-related gene expression were evaluated by quantitative real-time polymerase chain reaction and western blotting. Gallic acid effectively lowered SBP, regardless of the administration route (intraperitoneal or oral). L-NAME increased the left ventricular (LV) thickness without an increase in the total heart weight. Weekly echocardiography demonstrated that gallic acid significantly reduced LV posterior wall and septum thickness in chronic L-NAME mice from 3 to 7 weeks. The administration of gallic acid to mice showed a dual preventive and therapeutic effect on the L-NAME-induced LV remodeling. The effect was associated with the suppression of the gene expression of hypertrophy markers and the GATA-binding factor 6 (GATA6) transcription factor. Short-term or long-term treatment with gallic acid attenuated cardiac fibrosis and reduced the expression of histone deacetylase 1 and 2 in H9c2 cells and in rat primary cardiac fibroblasts, as well as in vivo. Small interfering RNA knockdown confirmed the association of these enzymes with L-NAME-induced cardiac remodeling and fibrosis. These results suggested that gallic acid may be a potential therapeutic agent for the treatment of cardiovascular diseases with hypertension and cardiac fibrosis.

The nephroprotective effects of ginkgo biloba extract (EGb761) against l-NG-nitroarginine methyl ester-induced hypertension in rats: role of oxidative stress and inflammatory markers

BackgroundGinkgo biloba extract 761 (EGb761) was studied for its nephroprotective effects in experimentally induced hypertension. Hypertension is increasingly a cause of end-stage renal diseases. Increased cytokine release and oxidative stress are mechanisms that appear to be involved in the pathogenesis of hypertensive renal damage. EGb has antioxidant and anti-inflammatory effects and can attenuate hypertensive renal damage.Methods and resultsMale adult Wistar rats were used in this study. Hypertension was induced in these rats by administering l-NG-nitroarginine methyl ester (l-NAME) (10 mg/kg/day, intraperitoneal) for 12 weeks. Another group of rats received l-NAME and EGb761 (100 mg/kg/day, orally) starting from the ninth week to the end of treatment. It was found that the blood pressure was reduced at the end of 12th week in rats treated with EGb761 compared with l-NAME-treated (hypertensive) rats. EGb761-treated rats showed lower renal tissue malondialdehyde level and renal tissue tumor necrosis factor-α level when compared with l-NAME-treated rats (hypertensive).ConclusionEGb761 has antihypertensive effect; it can protect the kidney from hypertension through the reduction of renal inflammation and oxidative stress.

Hypertensive heart disease

Hypertensive heart disease

Impact of T Lymphocytes on Cardiac Remodeling in Hypertension

In their intriguing article appearing in this issue of Hypertension , Yu et al1 provide evidence for a role of T lymphocytes in modulating cardiac matrix remodeling resulting from hypertension. The investigators compared the impact of comparable N G-nitro-l-arginine methyl ester (l-NAME)-induced hypertension on cardiac function and matrix composition among 3 strains of mice with widely different T-lymphocyte profiles. They found increased ventricular stiffness, accompanied by enhanced collagen deposition and cross-linking in the strain of mice that were Th2 dominant (BALB/c). In contrast, in mice that were T- (and B-) lymphocyte deficient (C57BL/6 SCID), hypertension resulted in a diminution of collagen content and cross-linking that was generally associated with heart dilation. No changes in ventricular stiffness or collagen were observed in mice that were Th1 dominant (C57BL/6 WT). Because these different responses of the heart to hypertension were observed under pre-existing dissimilar and extreme immune backgrounds, an obvious question is what impact, if any, T lymphocytes have on hypertension-associated cardiac remodeling in more common scenarios. Will it turn out that the well-established neurohormonal input into cardiac remodeling is actually an immunoneurohormal system or only that the neurohormonal component of remodeling is susceptible to modulation by extreme immune conditions? Other than this broad question, several specific questions come to mind from the work of Yu et al.1 First, how relevant is the use of l-NAME to induce hypertension and cardiac remodeling? Chronic pressure overload of the heart in animal models typically induces changes in the heart that include both increased extracellular matrix deposition and so-called compensatory left ventricular hypertrophy because of enlargement of individual …

Rho-kinase, a potential therapeutic target for the treatment of hypertension

Hypertension is a cardiovascular disorder characterized by increased peripheral vascular resistance and/or vascular structural remodeling. Recently, rapidly growing evidence from hypertensive animal models suggests that small GTPase Rho and its downstream effector, Rho-kinase, play an important role in the pathogenesis of hypertension. Activation of the Rho/Rho-kinase pathway is essential for smooth muscle contractility in hypertension. A greater RhoA expression and an enhanced RhoA activity have been observed in aortas of hypertensive rats, such as genetic spontaneously hypertensive rats and N(omega)-nitro-L-arginine methyl ester-induced hypertension. The enhanced RhoA expression and activity was already observed in young spontaneously hypertensive rats before the onset of hypertension. These results suggest that both genetic factors and blood pressure can upregulate RhoA expression. Moreover, Y-27632 or fasudil, the specific Rho-kinase inhibitors, markedly decreased blood pressure in various hypertensive model rats, but did not in normotensive animals. In addition, Rho-kinase inhibitors have been shown to inhibit hypertensive vascular lesion formation. Therefore, Rho-kinase inhibitors may have a therapeutic potential for the treatment of hypertensive patients.

Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy.

Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

Sodium sensitivity and sympathetic nervous system in hypertension induced by long-term nitric oxide blockade in rats.

1. Pharmacological inhibition of nitric oxide (NO) synthesis is known to produce acute and chronic hypertension in many animal species, but the underlying mechanisms mediating the hypertension are not completely understood. In particular, the pathogenetic roles of sodium sensitivity and the sympathetic nervous system in this model of hypertension are controversial. The present study was designed to test the hypothesis that long-term administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to male Sprague-Dawley rats would produce a sodium-sensitive hypertension and that the enhanced activity of the sympathetic nervous system in this type of hypertension contributes to the sodium sensitivity. 2. NG-Nitro-L-arginine methyl ester was added to drinking fluid for 8 weeks at a concentration of 16 mg/dL. Rats received tap water for the first 4 weeks of the study and were then divided into two groups and placed on either a normal or high sodium intake (ingestion of either tap water or 0.9% NaCl, respectively). Awake systolic blood pressure was measured by the tail-cuff method every week. Urinary excretion rates of the stable NO metabolites and catecholamines during NO synthesis inhibition were examined. 3. Long-term administration of L-NAME produced a marked and sustained elevation in arterial pressure without altering urine flow, or sodium excretion rate. NG-Nitro-L-arginine methyl ester-induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites NO2- and NO3- and was aggravated when rats drank 0.9% NaCl in place of tap water. Urinary excretion of adrenaline and noradrenaline, but not dopamine, in L-NAME-treated rats increased significantly within the first week of the study compared with control rats. L-Arginine (2 g/dL in drinking fluid) completely reversed the elevation of arterial pressure as well as the decrease in urinary NO2- and NO3- excretion and the increased urinary excretion of catecholamines associated with L-NAME treatment by 3 weeks of concomitant administration. 4. These results suggest that long-term inhibition of NO synthesis produces a sodium-sensitive hypertension and that changes in sympathetic nerve activity may, at least in part, contribute to the sodium sensitivity in this type of hypertension.

Calcitonin gene-related peptide is a depressor in NG-nitro-L-arginine methyl ester-induced hypertension during pregnancy.

Inhibition of nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME) increases blood pressure and fetal mortality in pregnant rats. We previously reported that administration of calcitonin gene-related peptide (CGRP) reduces the blood pressure and fetal death produced by L-NAME. To determine the hemodynamic role of endogenous CGRP in this setting, CGRP8-37, a CGRP receptor antagonist, was used. In addition, CGRP mRNA and peptide levels were determined in dorsal root ganglia. L-NAME or control rats had intravenous (for drug administration) and arterial (for continuous mean blood pressure monitoring) catheters surgically placed and were studied in the conscious unrestrained state. Baseline blood pressure was higher in the L-NAME than the control rats on days 19, 20, and 21 or pregnancy and postpartum day 1. Vehicle administration did not change blood pressure in any group, and CGRP8-37 (100 micrograms) did not change blood pressure in control groups. However, CGRP8-37 administration to the L-NAME rats further increased blood pressure (P < .05) on days 19 (8 +/- 1), 20 (12 +/- 2), and 21 (7 +/- 1) of gestation but was without effect on postpartum day 1. Furthermore, CGRP mRNA or peptide levels in dorsal root ganglia were not different between the L-NAME and control rats at any of the time points studied. These data indicate that in experimental preeclampsia, CGRP is playing a compensatory vasodilator role to attenuate the elevated blood pressure. The mechanism of this effect appears to be an enhanced vascular responsiveness to CGRP that is attenuated after the birth of pups.

Vascular reactivity and flow-pressure curve in isolated kidneys from rats with N-nitro-L-arginine methyl ester-induced hypertension.

The purpose of this study was to determine the contribution of the functional changes in resistance vessels to the hypertension induced by chronic nitric oxide synthase inhibition in rats. Another goal of this study was to evaluate whether this model of hypertension is accompanied by changes in the activity of endothelium-derived hyperpolarizing factor (EDHF). Hypertension was induced by long-term (6 weeks) oral administration of N-nitro-L-arginine methyl ester (L-NAME; 75 mg/100 ml in the drinking fluid). Vascular reactivity to vasoconstrictors (phenylephrine and barium chloride) and vasodilators (acetylcholine and nitroprusside) and the flow-pressure curve were examined in isolated perfused kidneys preparations. Vascular reactivity to vasoconstrictors and the flow-pressure curve were studied under basal conditions or after the infusion of L-arginine (100 mumol/l). The activity of EDHF was evaluated by comparing the dose-response curves for acetylcholine obtained in potassium chloride- and phenylephrine-preconstricted preparations. Kidneys from L-NAME-induced hypertensive rats showed increased sensitivity to vasoconstrictors with a greater duration of the pressor responses at high doses and markedly up-shifted flow-pressure curve in comparison with that obtained in control kidneys. These differences disappeared when the kidneys from control and L-NAME-treated rats were infused with L-arginine. The kidneys from L-NAME-treated rats also showed a decreased responsiveness to acetylcholine with an augmented reactivity to nitroprusside. The acetylcholine dose-response curve was reduced in control preparations and greatly attenuated in L-NAME-treated preparations when the renal vasculature was preconstricted with potassium chloride. The changes in vascular reactivity observed in L-NAME-induced hypertensive rats may play an important role in the pathogenesis of this type of hypertension. Moreover, it is also suggested that long-term nitric oxide inhibition may be associated with increased activity of EDHF.

Vascular structure in NG-nitro-L-arginine methyl ester-induced hypertension: methodological considerations for studies of small arteries in hypertension

Vascular structure in NG-nitro-L-arginine methyl ester-induced hypertension: methodological considerations for studies of small arteries in hypertension

6 Development of sudanophilic lesions along the renal preglomerular vasculature during prolonged NG-nitro-L-arginine methyl ester-induced hypertension in rats

6 Development of sudanophilic lesions along the renal preglomerular vasculature during prolonged NG-nitro-L-arginine methyl ester-induced hypertension in rats

Decreased cardiac baroreflex sensitivity is not due to cardiac hypertrophy in NG-nitro-L-arginine methyl ester-induced hypertension

To investigate the link between cardiac hypertrophy, elevated blood pressure level and baroreflex impairment, we assessed cardiac baroreflex function in a hypertensive model almost devoid of cardiac hypertrophy, obtained by nitric oxide synthesis inhibition. Thirteen adult male Wistar rats were treated orally with NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg per 24 h) for 4 weeks. Fifteen control rats received tap water. At the end of the treatment aortic blood pressure was recorded continuously and the baroreceptor-heart rate curve was assessed by bolus injections of phenylephrine and sodium nitroprusside (10 different doses of each). Mean blood pressure was higher in L-NAME rats than in control rats, whereas body weight was similar. Total heart weight and left ventricular weight did not differ between the groups. Cardiac baroreflex was reset in hypertensive rats, as indicated by a rightwards shift of the mean blood pressure-heart rate curve. Its gain was decreased significantly in L-NAME rats, whereas the heart rate range was not different between the two groups. L-NAME hypertensive rats exhibit an original impairment of cardiac baroreflex, characterized by a range-independent decreased gain which is not due to cardiac hypertrophy.