Effect of in vivo gene transfer of nNOS in the PVN on renal nerve discharge in rats

2002 ◽  
Vol 282 (2) ◽  
pp. H594-H601 ◽  
Author(s):  
Yi-Fan Li ◽  
Shyamal K. Roy ◽  
Keith M. Channon ◽  
Irving H. Zucker ◽  
Kaushik P. Patel
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Nadph Diaphorase ◽  
Sympathetic Outflow ◽  
Renal Nerve ◽  
Cultured Fibroblasts ◽  
Dose Dependent Increase ◽  
Nerve Discharge

The paraventricular nucleus (PVN) of the hypothalamus is known to be involved in the control of sympathetic outflow. Nitric oxide (NO) has been shown to have a sympathoinhibitory effect in the PVN. The goal of the present study was to examine the influence of overexpression of neuronal NO synthase (nNOS) within the PVN on renal sympathetic nerve discharge (RSND). Adenovirus vectors encoding either nNOS (Ad.nNOS) or β-galactosidase (Ad.β-Gal) were transfected into the PVN in vivo. Initially, the dose of adenovirus needed for infection was determined from in vitro infection of cultured fibroblasts. In Ad.nNOS-treated rats, the local expression of nNOS within the PVN was confirmed by histochemistry for NADPH-diaphorase-positive neurons. There was a robust increase in staining of NADPH-diaphorase-positive cells in the PVN on the side injected with Ad.nNOS. The staining peaked at 3 days after injection of the virus. In α-chloralose- and urethane-anesthetized rats, microinjection of N G-monomethyl-l-arginine (l-NMMA), a NO antagonist, into the PVN produced a dose-dependent increase in RSND, blood pressure, and heart rate. There was a potentiation of the increase in RSND, blood pressure, and heart rate due to l-NMMA in Ad.nNOS-injected rats compared with Ad.β-Gal-injected rats. These results suggest that the endogenous NO-mediated effect in the PVN of Ad.nNOS-treated rats is more effective in suppressing RSND compared with Ad.β-Gal-treated rats. These observations support the contention that an overexpression of nNOS within the PVN may be responsible for increased suppression of sympathetic outflow. This technique may be useful in pathological conditions know to have increased sympathetic outflow, such as hypertension or heart failure.

Effects of spinal cord transection on sympathetic discharge in decerebrate-unanesthetized cats

1989 ◽  
Vol 257 (6) ◽  
pp. R1506-R1511 ◽  
Author(s):  
L. C. Weaver ◽  
R. D. Stein
Keyword(s):  
Blood Pressure ◽  
Spinal Cord ◽  
Heart Rate ◽  
Spectral Analysis ◽  
Spinal Cord Transection ◽  
Renal Nerves ◽  
Frequency Range ◽  
Renal Nerve ◽  
Sympathetic Discharge ◽  
Nerve Discharge

Previous experiments in our laboratory have shown that discharge of splenic, mesenteric, and splanchnic nerves is well maintained after spinal cord transection in chloralose-anesthetized cats (8, 9, 11). The primary purpose of this investigation was to determine if maintained sympathetic discharge could be observed after spinal transection in the absence of chloralose anesthesia. In cats anesthetized with alphaxalone-alphadolone, changes in splanchnic discharge, blood pressure, and heart rate caused by decerebration and removal of the forebrain were observed. This procedure decreased blood pressure, increased heart rate, and had no immediate effect on sympathetic discharge or its rhythm (assessed by power density spectral analysis). One hour after decerebration and termination of anesthesia, splanchnic discharge had increased by approximately 36%. Next, effects of spinal cord transection on discharge of splanchnic, mesenteric, and renal nerves were observed in the decerebrate-unanesthetized cats. Splanchnic discharge decreased by 50%, mesenteric nerve discharge was unchanged, and renal nerve discharge decreased by 97%. Therefore, splanchnic nerve discharge was not as well maintained in decerebrate-unanesthetized cats as it had been in chloralose-anesthetized animals, and the remaining splanchnic discharge appeared to affect mesenteric nerves preferentially. Finally, spectral analysis of the splanchnic discharge demonstrated that before cord transection, most of the signal was in the 0- to 6-Hz frequency range, whereas after transection the proportion of signal in this frequency range was significantly reduced and the proportion in higher frequencies (7-25 Hz) was significantly increased. This loss of low-frequency rhythmicity is consistent with findings in our previous studies in chloralose-anesthetized cats.

Studies in vivo and in vitro of terbutaline-induced β-adrenoceptor desensitization in healthy subjects

1987 ◽  
Vol 72 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Arne Martinsson ◽  
Kjell Larsson ◽  
Paul Hjemdahl
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cyclic Amp ◽  
Sympathetic Nerve ◽  
Healthy Subjects ◽  
Plasma Concentrations ◽  
Plasma Noradrenaline ◽  
Binding Studies

1. β-Adrenoceptor function was studied in eight healthy subjects before, during and 24 and 72 h after cessation of 2 weeks continuous oral treatment with the β2-adrenoceptor agonist terbutaline (sustained release, 7.5 mg twice daily). In vivo, blood pressure, heart rate, plasma noradrenaline and plasma cyclic AMP responses to isoprenaline (0.01, 0.02 and 0.05 μg min−1 kg−1 intravenously) were related to the plasma concentrations of isoprenaline. For comparison, β2-adrenoceptor function was evaluated in lymphocytes in vitro by studies of isoprenaline-induced accumulation of cyclic AMP and radioligand binding studies using 125I-iodohydroxybenzylpindolol. 2. In vivo, the β2-mediated plasma cyclic AMP response to isoprenaline was markedly attenuated during terbutaline treatment and was still reduced by 38% (P < 0.05) 72h. after discontinuation of treatment. The blood pressure and heart rate responses to isoprenaline were unaffected by treatment. Isoprenaline-induced elevations of plasma noradrenaline concentrations were markedly reduced during terbutaline treatment. This indicates an attenuation of isoprenaline-induced increases in sympathetic nerve function and could explain why no attenuation of the isoprenaline-induced vasodilatation was observed. Thus, plasma cyclic AMP seems to be a better marker than diastolic blood pressure when evaluating β2-adrenoceptor responsiveness in vivo in man, since it is not influenced by counter-regulatory increases in sympathetic nerve activity and/or noradrenaline overflow from sympathetic nerves. 3. In lymphocytes, the isoprenaline-stimulated cyclic AMP accumulation was reduced by 75% and the β-adrenoceptor binding sites were reduced by 40% 12 h after dosing. Also the lymphocyte β2-adrenoceptors recovered slowly after withdrawal of treatment. Normal responsiveness was not restored within 72 h after the last dose of terbutaline. 4. Thus, we obtained evidence in vivo and in vitro showing a markedly attenuated β2-adrenoceptor function, which persisted at least 72 h after discontinuation of terbutaline treatment. The slow rate of resensitization of β2-adrenoceptors after withdrawal may have practical implications in the treatment of, for example, asthma, since a state of ‘physiological β2-adrenoceptor blockade’ seems to be produced by β2-agonist treatment.

Comparative studies on differential inhibition of the rennin–angiotensin system in the anesthetized guinea pig

1995 ◽  
Vol 73 (10) ◽  
pp. 1512-1518 ◽  
Author(s):  
J. Duan ◽  
J. Jaramillo ◽  
G. L. Jung ◽  
A. L. McLeod ◽  
B. H. Fernandas ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Guinea Pig ◽  
Small Animal ◽  
Angiotensin System ◽  
Renin Inhibitors ◽  
Arterial Blood ◽  
Effect Of Pd

The present study compares the hemodynamic effects and mechanisms of action of angiotensin II (AngII) antagonists, angiotensin converting enzyme (ACE) inhibitors, and renin inhibitors in the guinea pig, an animal with high similarity to primates in terms of in vitro and in vivo responses to several human renin inhibitors. Animals were anesthetized with urethane and ketamine. The carotid artery was catheterized for monitoring blood pressure and heart rate. After 30 min stabilization, drug (or vehicle) effects were monitored for 1 h following each increasing dose (i.v. bolus injection). Drugs tested include losartan, an AngII receptor antagonist; two renin inhibitors, BILA 2157 BS and PD-134672; and captopril, an ACE inhibitor. All drugs dose dependency decreased blood pressure. Diastolic blood pressure was reduced more than systolic blood pressure, suggestive of vasodilation. The maximum decrease (32 ± 6%, p < 0.05 vs. vehicle) in mean arterial blood pressure (MABP) by losartan was achieved with a dose of 1 mg/kg. A similar decrease in MABP was observed with renin inhibitors at a dose of 3 mg/kg, without affecting heart rate. A further increase in the dose of renin inhibitors (6 mg/kg) decreased not only blood pressure but also heart rate. Captopril decreased MABP with a maximum of 48 ± 3% (p < 0.05 vs. vehicle, losartan, and PD-134672). In the presence of HOE-140, a bradykinin antagonist, the MABP decrease by captopril was only 35 ± 4%, (p < 0.05 vs. captopril alone). Bilateral nephrectomy reduced the peak MABP effect of PD-134672 by 67%, while the effects of captopril on MABP were affected to a lesser degree (57%). Therefore, captopril remains more effective in reducing MABP (p < 0.05 vs. that of PD-134672). These results suggest that renin inhibitors and AngII antagonists act more specifically on the rennin–angiotensin system cascade, while captopril acts partially by a bradykinin-dependent mechanism. The small animal model described provides a novel tool for the comparative pharmacologic assessment of different rennin–angiotensin system inhibitors.Key words: blood pressure, guinea pig, rennin–angiotensin system, rennin–angiotensin system inhibition.

scholarly journals Effect of chronic IL-6 infusion on acute pressor responses to vasoconstrictors in mice

2007 ◽  
Vol 293 (3) ◽  
pp. H1745-H1749 ◽  
Author(s):  
Erika I. Boesen ◽  
David M. Pollock
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Heart Rate Response ◽  
Blood Pressure Response ◽  
Ang Ii ◽  
Pressor Responses ◽  
Autonomic Reflexes ◽  
Blood Pressure Responses

Interleukin (IL)-6 has been implicated as a contributing factor in the pathogenesis of hypertension, although the mechanisms involved are unclear. Studies conducted in vitro suggest that IL-6 may have a direct effect on vascular tone and may modulate constrictor responses to agonists. Whether this effect can be observed in vivo is unknown. Therefore, mice were treated with either IL-6 (16 ng/h sc) or vehicle for 14 days, and the acute blood pressure and heart rate responses to endothelin (ET)-1, angiotensin II (ANG II), and phenylephrine (PE) were assessed under isoflurane anesthesia. Blood pressure responses to ET-1 were identical in vehicle- and IL-6-infused mice, both in the presence and the absence of ganglion blockade with chlorisondamine. The fall in heart rate during ET-1 responses was significantly attenuated in IL-6-infused mice with autonomic reflexes intact (vehicle vs. IL-6, P < 0.05 at 1 and 3 nmol/kg of ET-1), but this difference was not observed after ganglionic blockade. Both blood pressure and heart rate responses to ANG II were indistinguishable between IL-6- and vehicle-infused mice, as were responses to PE except for a significant increase in the blood pressure response and decrease in the heart rate response in IL-6-infused mice observed only at the highest dose of PE (300 μg/kg; P < 0.05). These findings show that, despite what might be predicted from studies conducted in vitro, chronic exposure to elevated plasma IL-6 concentrations in itself does not predispose the mouse to enhanced responsiveness to vasoconstrictors in vivo.

Effect of nitric oxide within the paraventricular nucleus on renal sympathetic nerve discharge: role of GABA

1998 ◽  
Vol 275 (3) ◽  
pp. R728-R734 ◽  
Author(s):  
Kun Zhang ◽  
Kaushik P. Patel
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sympathetic Nerve ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve ◽  
Arterial Blood ◽  
Gaba System ◽  
Renal Sympathetic ◽  
Nerve Discharge

Both nitric oxide (NO) and GABA are known to provide inhibitory inputs to the paraventricular nucleus (PVN) of the hypothalamus and are involved in the control of sympathetic outflow. The purpose of the present study was to examine the interaction of NO and GABA in the regulation of renal sympathetic nerve activity in rats. The responses of renal nerve activity, blood pressure, and heart rate to microinjection of sodium nitroprusside (SNP), an NO donor, into the PVN were measured in the presence and absence of blockade of the GABA system (bicuculline; 2 nmol). Microinjection of SNP (50, 100, and 200 nmol) into the PVN elicited significant decreases in renal nerve discharge, arterial blood pressure, and heart rate, reaching −36.4 ± 9.7%, −11 ± 5 mmHg, and −34 ± 14 beats/min, respectively, at the highest dose. These responses were eliminated by blockade of the GABA system. Conversely, microinjection of N ω-nitro-l-arginine methyl ester (l-NAME; 50, 100, and 200 nmol) elicited significant increases in the renal sympathetic nerve discharge, arterial blood pressure, and heart rate, reaching 88.9 ± 16.6%, 9 ± 1 mmHg, and 29 ± 9 beats/min, respectively, at the highest dose. These sympathoexcitatory responses were masked by prior blockade of the GABA system with bicuculline. The sympathoexcitatory effect of l-NAME was also eliminated by activation of the GABA system with muscimol. In conclusion, our data indicate that the inhibitory effect of endogenous NO within the PVN on the renal sympathetic nerve activity is mediated by GABA.

scholarly journals Vasorelaxant and Hypotensive Effects of Jaboticaba Fruit (Myrciaria cauliflora) Extract in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Daniela Medeiros Lobo de Andrade ◽  
Carolina de Fátima Reis ◽  
Patrícia Ferreira da Silva Castro ◽  
Leonardo Luiz Borges ◽  
Nathalia Oda Amaral ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Femoral Vein ◽  
Soluble Guanylyl Cyclase ◽  
Aortic Blood Flow ◽  
Aortic Blood ◽  
Cox Inhibitor

This study’s aim was to determine the effect of hydroalcoholic extract ofM. cauliflora(HEMC) on vascular tension and blood pressure in rats. In ourin vitrostudies using precontracted isolated aortas from rats, HEMC and acetylcholine (positive control) induced relaxation only in vessels with endothelium. Pretreatment with L-NAME (NO synthase inhibitor) or ODQ (soluble guanylyl cyclase (sGC) inhibitor) abolished the HEMC-induced relaxation. The treatment with MDL-12,330A (adenylyl cyclase (AC) inhibitor) or diclofenac (COX inhibitor) reduced HEMC-induced vasorelaxation. The blockade of muscarinic andβ-adrenergic receptors (by atropine and propranolol, resp.) did not promote changes in HEMC-induced vasorelaxation. In ourin vivostudies, catheters were inserted into the right femoral vein and artery of anesthetized rats for HEMC infusion and the measurement of blood pressure, heart rate, and aortic blood flow. The intravenous infusion of HEMC produced hypotension and increased aortic blood flow with no changes in heart rate. These findings showed that HEMC induces endothelium-dependent vascular relaxation and hypotension with no alteration in heart rate. The NO/sGC/cGMP pathway seems to be the main cellular route involved in the vascular responsiveness.

Effects of β-blockers on the Concentration and Oxidizability of Plasma Lipids

1998 ◽  
Vol 94 (6) ◽  
pp. 573-578 ◽  
Author(s):  
Simon B. Dimmitt ◽  
Peta D. Williams ◽  
Kevin D. Croft ◽  
Lawrence J. Beilin
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Plasma Lipids ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Protective Effects ◽  
Β Blocker ◽  
Β Blockers

1. β-blockers improve morbidity and mortality after myocardial infarction, probably by several mechanisms. We investigated potentially relevant effects of β-blockers in vivo and in vitro on plasma lipid oxidizability. Forty-two healthy men were randomized to receive placebo (13), metoprolol (14) or propranolol (15). 2. At 4 weeks, the effects on heart rate, blood pressure and lipids appeared similar and subjects taking a β-blocker were combined. Compared with placebo, those on a β-blocker gained 0.5 kg in weight (P = 0.04), heart rate fell from 63 to 52 beats/min (P < 0.0001) and blood pressure fell from 116/74 to 113/69 mmHg (P < 0.005); high-density lipoprotein (HDL)-cholesterol fell from 1.26 to 1.11 mmol/l (P = 0.005), there being no change in the ratio of free to esterified cholesterol in HDL, and there was an apparent rise in serum triacylglycerols from 1.18 to 1.43 mmol/l (P = 0.15 when adjusted for weight gain). Low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) did not change. In this study, the oxidizability of LDL was unaffected by β-blocker therapy. β-blockade was not associated with any change in LDL fatty acid profile, or β-carotene or α-tocopherol content which might account for the reduced LDL oxidizability previously reported in patients treated with β-blockers. Furthermore, neither atenolol nor propranolol, at concentrations up to 100 μmol/l, had any effect on in vitro oxidizability of LDL obtained from healthy volunteers. 3. In contrast to the favourable haemodynamic effects conferred by β-blockers, the effects on weight and serum triacylglycerols and HDL-cholesterol appear to be adverse and we did not demonstrate any changes in lipid oxidizability which might be relevant to the protective effects of β-blockers in patients with coronary disease.

Hemodynamic Effects and Hypertrophy-Inducing Potential of D- and L-Thyroxine

1974 ◽  
Vol 52 (3) ◽  
pp. 496-499 ◽  
Author(s):  
Glenn B. Axelrod ◽  
April A. Whitbeck ◽  
Jules Cohen
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Protein Synthesis ◽  
Cardiac Output ◽  
Cardiac Hypertrophy ◽  
Hemodynamic Effects ◽  
Heart Mass ◽  
Growth Promoting

The capacities of D- and L-thyroxine to induce cardiac hypertrophy have been studied in rats as a function of the extent of the circulatory changes produced by the two isomers. D-Thyroxine had no effect on blood pressure, heart rate, or cardiac output, but significantly increased heart mass. L-Thyroxine had a small effect on mean blood pressure, a larger effect on heart rate, and caused a large increase in cardiac output. The closest parallels were between effects on heart rate and on heart growth. In companion experiments, D- and L-thyroxine were shown to be equipotent in stimulating atrial protein synthesis in vitro. The growth-promoting effects of both D- and L-thyroxine, therefore, seem largely direct and independent of the large increase in flow work produced by administration of the L-isomer in vivo.

The Involvement of Platelets and the Coronary Vasculature in Collagen-Induced Sudden Death in Rabbits

1985 ◽  
Vol 53 (01) ◽  
pp. 070-074 ◽  
Author(s):  
G Mallarkey ◽  
G M Smith
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Platelet Count ◽  
Sudden Death ◽  
Myocardial Ischaemia ◽  
Plasma Levels ◽  
Sodium Citrate ◽  
Plasma Samples ◽  
Calcium Entry Blockers

SummaryThe mechanism of collagen-induced sudden death in rabbits was studied by measuring blood pressure (BP), heart rate, ECG, the continuous platelet count and the plasma levels of thromboxane B2 (TxB2) and 6-keto prostaglandin Fia (6-keto PGF1α). Death was preceded by myocardial ischaemia and a sharp fall in BP which occurred before any fall in platelet count was observed. The calcium entry blockers (CEBs), verapamil, nifedipine and PY 108-068 protected the rabbits from sudden death without any significant effect on the decrease in the platelet count or increase in plasma TxB2 levels. 6-keto PGF1α could not be detected in any plasma samples. Indomethacin and tri-sodium citrate also protected the rabbits but significantly reduced the fall in platelet count and plasma TxB2. In vitro studies on isolated aortae indicated that verapamil non-specifically inhibited vasoconstriction induced by KC1, adrenaline and U46619 (a thromboxane agonist). It is concluded that CEBs physiologically antagonize the vasoconstricting actions of platelet-derived substances and that it is coronary vasoconstriction that is primarily the cause of death.

Cardiovascular Effects of Micromeria graeca (L.) Benth. ex Rchb in Normotensive and Hypertensive Rats

2020 ◽  
Vol 20 (8) ◽  
pp. 1253-1261
Author(s):  
Mourad Akdad ◽  
Mohamed Eddouks
Keyword(s):  
Blood Pressure ◽  
Cardiovascular System ◽  
Arterial Blood Pressure ◽  
Antihypertensive Activity ◽  
Computer Assisted ◽  
Hypertensive Rats ◽  
Vasorelaxant Effect ◽  
Arterial Blood

Aims: The present study was performed in order to analyze the antihypertensive activity of Micromeria graeca (L.) Benth. ex Rchb. Background: Micromeria graeca (L.) Benth. ex Rchb is an aromatic and medicinal plant belonging to the Lamiaceae family. This herb is used to treat various pathologies such as cardiovascular disorders. Meanwhile, its pharmacological effects on the cardiovascular system have not been studied. Objective: The present study aimed to evaluate the effect of aqueous extract of aerial parts of Micromeria graeca (AEMG) on the cardiovascular system in normotensive and hypertensive rats. Methods: In this study, the cardiovascular effect of AEMG was evaluated using in vivo and in vitro investigations. In order to assess the acute effect of AEMG on the cardiovascular system, anesthetized L-NAME-hypertensive and normotensive rats received AEMG (100 mg/kg) orally and arterial blood pressure parameters were monitored during six hours. In the sub-chronic study, rats were orally treated for one week, followed by blood pressure assessment during one week of treatment. Blood pressure was measured using a tail-cuff and a computer-assisted monitoring device. In the second experiment, isolated rat aortic ring pre-contracted with Epinephrine (EP) or KCl was used to assess the vasorelaxant effect of AEMG. Results: Oral administration of AEMG (100 mg/kg) provoked a decrease of arterial blood pressure parameters in hypertensive rats. In addition, AEMG induced a vasorelaxant effect in thoracic aortic rings pre-contracted with EP (10 μM) or KCl (80 mM). This effect was attenuated in the presence of propranolol and methylene blue. While in the presence of glibenclamide, L-NAME, nifedipine or Indomethacin, the vasorelaxant effect was not affected. Conclusion: This study showed that Micromeria graeca possesses a potent antihypertensive effect and relaxes the vascular smooth muscle through β-adrenergic and cGMP pathways.

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