Biomedical subjects

M Gerová

Publications and source records attributed to M Gerová.

At least 19 recordsLinked to original sources

PubMed2006

Systemic blood pressure response to the inhibition of two hyperpolarizing pathways: a comparison to NO-synthase inhibition.

The impact on blood pressure of two vasodilating mechanisms, underlied by vascular smooth muscle hyperpolarization, was studied and compared to that induced by nitric oxide NO mechanism. Systemic blood pressure, after inhibitory intervention in arachidonic acid metabolism cytochrome P-450 inhibition by miconazole 0.5 mg/100 g b.w. , one of the hyperpolarizing pathways, did not change. After the inhibition of the action voltage-dependent K(+) channels operator by 4-aminopyridine 0.1 mg/100 g b.w. , the other hyperpolarizing pathway, blood pressure declined slightly from 132.3+/-3.2 mm Hg to 116.5+/-5.0 mm Hg, P<0.05 . Inhibition of nitric oxide production L-NAME 5 mg/100 g b.w. increased blood pressure considerably 123.5+/-2.7 mm Hg to 155.4+/-3.1 mm Hg, P<0.001 . After inhibition of the hyperpolarizing pathway by miconazole, hypotension induced by acetylcholine (Ach, 10 microg represented 63.0+/-1.9 mm Hg vs control value 78.6+/-5.2 mm Hg P<0.001 , by bradykinin (BK) 100 microg 59.4+/-3.9 mm Hg vs control value 71.2+/-6.1 mm Hg P<0.05 . After inhibition of the hyperpolarizing pathway by 4-aminopyridine, hypotension induced by ACh 10 microg achieved 64.6+/-2.5 mm Hg vs control value 78.4+/-2.8 mm Hg P<0.001 and that induced by BK 100 microg 56.6+/-5.3 mm Hg vs control value 72.3+/-2.5 mm Hg P<0.001 . ACh or BK hypotension after the inhibition of the above hyperpolarizing pathways was significantly attenuated. On the contrary, after NO-synthase inhibition the hypotension to ACh was significantly enhanced. Blood pressure decrease after ACh 10 microg hypotension was 91.8+/-4.1 mm Hg vs control value 79.3+/-3.3 mm Hg P<0.01 , and after BK 100 microg it was 78.4+/-7.1 mm Hg vs control value 68.3+/-5.2 mm Hg. A different basal BP response, but equally attenuated hypotension to Ach and BK, was detected after the inhibition of two selected hyperpolarizing pathways. In cotrast, the inhibition of NO production elicited an increase in systemic BP and augmentation of ACh and BK hypotension. The effectiveness of further hyperpolarizing mechanisms in relation to systemic BP regulation and nitric oxide level remains open.

4-Aminopyridine↗

PubMed2005

Acetylcholine and bradykinin enhance hypotension and affect the function of remodeled conduit arteries in SHR and SHR treated with nitric oxide donors.

Discrepancy was found between enhanced hypotension and attenuated relaxation of conduit arteries in response to acetylcholine (ACh) and bradykinin (BK) in nitric oxide (NO)-deficient hypertension. The question is whether a similar phenomenon occurs in spontaneously hypertensive rats (SHR) with a different pathogenesis. Wistar rats, SHR, and SHR treated with NO donors [molsidomine (50 mg/kg) or pentaerythritol tetranitrate (100 mg/kg), twice a day, by gavage] were studied. After 6 weeks of treatment systolic blood pressure (BP) was increased significantly in experimental groups. Under anesthesia, the carotid artery was cannulated for BP recording and the jugular vein for drug administration. The iliac artery was used for in vitro studies and determination of geometry. Compared to control, SHR showed a significantly enhanced (P < 0.01) hypotensive response to ACh (1 and 10 microg, 87.9 +/- 6.9 and 108.1 +/- 5.1 vs 35.9 +/- 4.7 and 64.0 +/- 3.3 mmHg), and BK (100 microg, 106.7 +/- 8.3 vs 53.3 +/- 5.2 mmHg). SHR receiving NO donors yielded similar results. In contrast, maximum relaxation of the iliac artery in response to ACh was attenuated in SHR (12.1 +/- 3.6 vs 74.2 +/- 8.6% in controls, P < 0.01). Iliac artery inner diameter also increased (680 +/- 46 vs 828 +/- 28 microm in controls, P < 0.01). Wall thickness, wall cross-section area, wall thickness/inner diameter ratio increased significantly (P < 0.01). No differences were found in this respect among SHR and SHR treated with NO donors. These findings demonstrated enhanced hypotension and attenuated relaxation of the conduit artery in response to NO activators in SHR and in SHR treated with NO donors, a response similar to that found in NO-deficient hypertension.

Acetylcholine↗

PubMed2004

Hypotrophy of conduit artery walls of the offspring of nitric oxide-defective rats.

The objective of the present study was to investigate the structure of the arterial walls of the offspring stemming from nitric oxide (NO)-defective hypertensive parents. The parents were treated with NG-nitro-L-arginine methyl ester (40 mg kg-1 day-1) for 5 weeks. Blood pressure was measured noninvasively in six 30-day-old rats and nine age-matched controls. The cardiovascular system was perfused with glutaraldehyde at 120 mmHg. The thoracic aorta and carotid artery were processed for electron microscopy, and geometry was determined by light microscopy. Endothelial cells, smooth muscle cells (SMC) and extracellular matrix (ECM) were determined by the point counting method in electron micrographs of the carotid artery. The blood pressure of experimental offspring was 150.0 +/- 2.3 vs 104.6 +/- 2.1 mmHg (P < 0.01) for the controls and their heart/body weight ratio of 3.9 +/- 0.1 vs 4.4 +/- 0.2 (P < 0.05) for the controls indicated cardiac hypotrophy. The wall thickness (tunica intima and media) of the thoracic aorta and carotid artery of experimental offspring was decreased to 78.9% (P < 0.01) and 83.8% (P < 0.01), respectively, compared to controls, as confirmed by a respective cross-sectional area of 85.3% (P < 0.01) and 84.1% (P < 0.01). The wall thickness/inner diameter ratio was reduced to 75% (P < 0.01) in the thoracic artery and to 81.5% (P < 0.01) in the carotid artery. No change in endothelial cell volume density or ECM was observed in the tunica intima of the carotid artery, and SMC volume density was lower in the tunica media (37.6 +/- 0.9 vs 44.7 +/- 1.1% for controls, P < 0.01), indicating compromised SMC development. Interference with arginine metabolism, a decrease in NO, and other factors are possible mechanisms underlying the structural alterations of the cardiovascular system of offspring from NO-defective hypertensive rats.

Animals↗

PubMed2004

Hypotensive effect of agmatine, arginine metabolite, is affected by NO synthase.

The metabolites of arginine were recently shown to be involved in cardiovascular control. The study addresses the general cardiovascular response of anaesthetized rats to agmatine, a decarboxylated arginine. The relation between two arginine metabolic pathways governed by arginine decarboxylase and nitric oxide synthase was investigated. Intravenous administration of agmatine 30 and 60 microM/0.1 ml saline elicited remarkable hypotension of 42.6+/-4.6 and 70.9+/-6.5 mm Hg, respectively. The hypotension was characterized by long duration with half-time of return 171.6+/-2.9 and 229.2+/-3.8 s, respectively. The time of total blood pressure BP recovery was about 10 min. Dose-dependent relaxation to agmatine was also found in aorta rings in vitro. Both doses of agmatine administered 60-180 min after NO synthase inhibition L-NAME 40 mg/kg i.v. caused greater hypotension 59.0+/-7.6 and 95.8 8.8 mm Hg P<0.01 both compared to animals with intact NO synthase, but this was accompanied by a significant shortening of the half-time of BP return. If agmatine was administered to hypertensive NO-deficient rats treated with 40 mg/kg/day L-NAME for 4 weeks, similar significant enhancement of hypotension was observed at both agmatine doses, again with a significant shortening of half-time of BP return. It can be summarized that the long-lasting hypotension elicited by agmatine was amplified after acute or chronic NO synthase inhibition, indicating a feedback relation between the two metabolic pathways of arginine.

Agmatine↗

PubMed2002

Cardiovascular system of offsprings of hypertensive rats with defective nitric oxide production.

The question was addressed of how nitric oxide synthase (NO synthase) inhibition-induced hypertension in rat parents would affect the cardiovascular system in their offsprings. Two experimental groups were set up: Group I -- offsprings of parents who had both been administered NO synthase inhibitor L-nitro-arginine methyl ester (L-NAME 40 mg/kg/day) for 5 weeks, the treatment of dams continued till week 12. Group II -- offsprings fed by dams administered L-NAME after delivery only for a period of 4 weeks. Control age-matched offsprings formed the third group. Blood pressure and heart rate in parents and in 3-week-old offsprings were determined noninvasively. In the offsprings, body and heart weight were measured and the heart/body weight ratio (HW/BW) was calculated. The NO synthase activity, and also ornithine decarboxylase activity as a marker of polyamine production, were determined in the heart. The acetylcholine-induced relaxation of aortic rings was also followed. A marked blood pressure increase with a tendency to a decreased heart rate was found in the offsprings of Group I. A significant decrease in heart weight and body weight with a decreased HW/BW ratio indicated cardiac hypotrophy that contrasted with the decrease in NO synthase activity and increase in ornithine decarboxylase activity in the heart. Noteworthy was also the finding of completely preserved relaxation of the aorta to acetylcholine. Offsprings of Group II were similarly characterized by significantly higher blood pressure, a tendency to decreased heart rate, a decrease in heart weight, but not of the HW/BW ratio. The contrasting findings of heart weight decrease on the one hand and NO synthase activity decrease and ornithine decarboxylase increase on the other, were also found in this group. Full relaxation of the aorta to acetylcholine was preserved. It can be concluded that remarkable alterations in the cardiovascular system were found in offsprings of hypertensive NO compromised parents.

Acetylcholine↗

PubMed2002

Short-term NO synthase inhibition and the ATP affinity of cardiac Na,K-ATPase.

It was previously shown that 4 hours lasting inhibition of nitric oxide synthesis by administration of an L-arginine analogue, the A(G)-nitro-L-arginine methyl ester (L-NAME) changed the affinity of the Na-binding site of Na,K-ATPase thus resulting in elevation of enzyme activity especially at higher concentrations of sodium. Using the same experimental model, we focused our attention in the present study to the question of binding of ATP to the enzyme molecule in the left ventricle (LV), ventricular septum (S) and the right ventricle (RV) of the dog heart. Activation of the enzyme by increasing concentrations of ATP revealed a significant increase of the Vmax only in septum (by 38 %). The K(M) increased significantly in septum (by 40 %) and in left ventricle (by 56 %) indicating an altered sensitivity of the ATP-binding site of Na,K-ATPase in the hearts of NO-deficient animals. The alterations of Na,K-ATPase in its ability to bind and hydrolyze ATP are localized to the tissue surrounding the cavity of the left ventricle.

Adenosine Triphosphate↗

PubMed2001

Efficiency of NO donors in substituting impaired endogenous NO production: a functional and morphological study.

Two exogenous NO donors were used to act as substitutes for impaired endogenous nitric oxide (NO) production due to inhibition of NO synthase in rats. Six weeks' lasting inhibition of NO synthase by NG-nitro-L-arginine methyl ester (L-NAME) induced stabilized hypertension. Simultaneously administered isosorbide-5-mononitrate did not prevent the development of hypertension. Molsidomine, administered concomitantly with L-NAME, significantly attenuated the BP increase. However, BP was still found to be moderately increased compared to the initial values. Remarkable alterations in the geometry of the aorta, carotid and coronary artery found in NO-deficient hypertension were prevented in rats administered L-NAME plus molsidomine at the same time. In spite of 6 weeks' lasting inhibition of NOS, the NOS activators acetylcholine and bradykinin induced BP decrease; the maximum hypotensive value did not differ from the values recorded in the controls or in animals treated with L-NAME plus molsidomine. Notably enough, the hypotension was similar to that found in rats administered L-NAME alone for six weeks. After NO synthase inhibition, Isosorbide-5-mononitrate does not substitute and molsidomine substitute only partially the impaired endogenous NO production.

Acetylcholine↗

PubMed2000

Nitric oxide-compromised hypertension: facts and enigmas.

NO concentration in the femoral artery and femoral vein of anesthetized dogs was found to be 154.2+/-5.6 nM and 90.0+/-12 nM, respectively. Inhibition of NO synthase (NOS) slightly decreased the basal NO concentration in femoral artery from 154.2+/-5.6 to 137.2+/-3.3 nM. Acetylcholine-induced increase in NO concentration was slightly but still significantly attenuated, suggesting that very probably L-NAME did not inhibit all sources of nitric oxide (NO). Local NOS inhibition in the posterior hypothalamus dose-dependently increased systemic blood pressure (BP) in rats. Short-term general NOS inhibition in anesthetized dogs increased diastolic BP but not systolic BP. The heart rate after one-hour down-fluctuation returned to initial values. Proteosynthesis in the myocardium and both branches of the left coronary artery increased, but this was not supported by polyamines, since the activity of ornithine decarboxylase declined. Long-term general NOS inhibition elicited a sustained BP increase, a decrease in heart rate, cardiac hypertrophy and an increase in wall thickness of the coronary and carotid artery. The results indicate that NO deficiency itself plays a role in proteosynthesis and cardiac hypertrophy, in spite of relatively small increase in diastolic blood pressure and no change in systolic blood pressure, at least after an acute L-NAME administration. The hypotension response to acetylcholine and bradykinin studied in anesthetized NO-compromised rats, was unexpectedly enhanced. The elucidation of this paradoxical phenomenon will require further experiments.

Animals↗

PubMed2000

Short-term NO synthase inhibition and the Na+-binding properties of cardiac Na,K-ATPase.

It is known that hypertension is accompanied by increased [Na+]i. The functional properties of Na,K-ATPase, which transports the Na+ out and K+ into myocardial cells during the relaxation phase, were investigated in the left ventricle (LV), septum (SV) and the right ventricle (RV) of anesthetized dogs with moderate acute blood pressure elevation elicited by short-term (4-hour) NO synthase inhibition. The NO-insufficiency was induced by administration of an L-arginine analogue, the N(G)-nitro-L-arginine methyl ester (L-NAME). Concerning the function of Na,K-ATPase under the conditions of lowered NO synthesis, we focused our attention to the binding of Na+ to the enzyme molecule. Activation of the enzyme by increasing Na+ concentrations revealed significant changes in both the maximal velocity (Vmax) and the affinity for Na+ (K(Na)) in all investigated heart sections. The Vmax increased by 27% in LV, by 87% in SV and by 58% in RV. The K(Na) value increased by 86% in LV, by 105% in SV and by 93% in RV, indicating an apparent decrease in the sensitivity of the Na+-binding site in the Na,K-ATPase molecule. This apparently decreased pump affinity for Na+ together with the increase of Vmax suggest that, during the short-term inhibition of NO synthesis, the Na,K-ATPase is capable of extruding the excessive Na+ from the myocardial cells more effectively at higher [Na+]i, as compared to the Na,K-ATPase of control animals.

Animals↗

PubMed1999

Acetylcholine and bradykinin induce paradoxically amplified hypotensive response in hypertensive NO-deficient rats.

The hypotensive response to acetylcholine and bradykinin was studied in rats with NO synthase activity inhibited for a short period of 2 h or a long period of 6 weeks. N(G)-nitro-L-arginine-methyl ester (L-NAME) was used as NO synthase inhibitor (given in a dose of 50 mg/kg either into the jugular vein, or daily in drinking water). Blood pressure was measured in the right carotid artery by a Statham pressure transducer in acute experiments, and on the tail artery by the plethysmographic method weekly in chronic experiments. During both the short- and long-lasting NO synthase inhibition blood pressure rose significantly. The heart rate decreased significantly in rats treated with L-NAME for 6 weeks. Surprisingly, the hypotensive responses to acetylcholine and bradykinin were present in both experimental groups. Paradoxically, the hypotensive responses to all three doses of acetylcholine were remarkably enhanced in rats with NO synthase inhibition lasting 6 weeks, in comparison to both age-matched controls and to rats subjected to short-lasting NO synthase inhibition. The blockade of muscarinic receptors by atropine abolished the hypotensive response to acetylcholine but not to bradykinin. The hypothetical mechanisms underlying this unexpected paradoxical phenomenon of cardiovascular control are discussed.

Acetylcholine↗

PubMed1998

Early changes of protein synthesis in myocardium and coronary arteries induced by NO synthase inhibition.

The question was addressed whether short-term (4 hour) NO deficiency, inducing an increase in blood pressure in anaesthetized dogs, does influence proteosynthesis in the myocardium and coronary arteries. A potentially positive answer was to be followed by the study of the supporting role of ornithine decarboxylase for the polyamines pathway. N(G)-nitro-L-arginine-methyl ester (L-NAME) (50 mg/kg per hour) was administered i.v. to inhibit NO synthase. After the first L-NAME dose diastolic blood pressure increased from 131.8+/-2.0 to 149.4+/-3.9 mm Hg (p<0.001) and was maintained at about this level till the end of the experiment. Systolic blood pressure only increased after the first dose (from 150.8+/-1.1 to 175.0+/-5.8 mm Hg, p<0.01), returning thereafter to the control level. Similarly, the heart rate declined only after the first dose (from 190.4+/-5.3 to 147.6+/-4.5 beats/min, p<0.01). Total RNA concentrations increased in the left cardiac ventricle (LV), the left anterior descending coronary artery (LADCA) and left circumflex coronary artery (LCCA) by 15.9+/-0.7, 29.7+/-1.3 and 17.6+/-1.0%, p<0.05, respectively. The same applied to [14C]leucine incorporation (by 86.5+/-5.0, 33.5+/-2.6, 29.3+/-4.1%, p<0.05, respectively). The above parameters indicated an increase of proteosynthesis in the LV myocardium and both coronary arteries LADCA and LCCA after short-term NO deficiency. Surprisingly, the ornithine decarboxylase activity in the LV myocardium decreased significantly by 40.2+/-1.6% (p<0.01) but the changes were not significant in the coronary arteries. This unexpected finding makes the role of polyamines in increasing proteosynthesis during a pressure overload due to NO deficiency questionable.

Animals↗

PubMed1998

NO concentration in the periendothelial area of the femoral artery of the dog measured in vivo.

.NO concentration was measured in the periendothelial area of the femoral artery by Malinski's porphyrinic .NO sensor in seven anaesthetized dogs. The basal concentration was 154.2 +/- 5.6 nM and two-minute intraarterial infusions of acetylcholine (3-4 micrograms/ml/min) or bradykinin (30-40 ng/ml/min) increased this value significantly to 204.3 +/- 16.4 and 266.5 +/- 16.4 nM (P < 0.01), respectively. Inhibition of .NO synthase by L-NAME (50 mg/kg) declined the basal .NO concentration only to 137.2 +/- 3.3 nM (P < 0.01). Subsequent administration of acetylcholine and bradykinin attenuated significantly the increase in .NO concentration. Surprisingly, both agonists still induced a significant increase of .NO concentration by 125.3 +/- 8.3 and 156.6 +/- 26.9 nM, respectively (P < 0.01). One of the possible explanations may be that besides arginine-citrulline plus the .NO pathway other sources of .NO could be involved in the high level of .NO after .NO synthase blockade by L-NAME.

Acetylcholine↗

PubMed1997

Developmental dynamics of endothelial and neurogenic control of canine thoracic aorta.

The purpose of the study was to confront the range of endothelial relaxation and neurogenic contraction of the thoracic aorta in fetuses (1 week before birth), puppies (1, 2, 4 and 6 weeks old), and in adult dogs. Isometric tension of aortic rings was monitored in organ bath. Acetylcholine-induced dose-dependent relaxation of aortic rings precontracted by phenylephrine was pronounced already in fetuses and puppies and significantly larger than in adults. Indomethacin, a cyclooxygenase inhibitor, did not affect the magnitude of aortic relaxation to acetylcholine. Transmural nerve stimulation induced but very slight contractions of the thoracic aorta in fetuses, while in puppies the extent of contractions was increasing with increasing age, reaching its maximum in adults. Contractile responses of aortic rings induced by KCl were fully detectable in fetuses and puppies and increased with increasing age of the animals. Thus in ontogenesis, the extent of endothelium-dependent relaxation and neurogenic contraction of the thoracic aorta displayed an opposite trend. The acetylcholine-induced relaxation was fully operative already in fetuses and puppies and its extent was declining toward adulthood, whereas the neurogenic contraction was hardly detectable in fetuses, increasing in puppies, and showed the highest values in adults.

Acetylcholine↗

PubMed1997

Dynamics of endothelium-muscle cell contacts in the coronary artery of the dog in ontogeny.

The myo-endothelial area in the coronary artery conduit was described in 3 developmental stages: in fetuses, newborns, and adult dogs. Transmission and scanning electron microscopy were used for the study, and morphometry was used for quantitative evaluation. In all three stages, the internal elastic lamina was found to be fenestrated. Endothelial cells and smooth muscle cells (SMC) approached the fenestrae, and protrusions of one or both cells entered into the fenestrae. In some places contacts between endothelial and SMC were found. The patterns of mutual approaches of smooth muscle and endothelial cells, as well as the entering into the fenestrae were similar in all three stages. The myo-endothelial contacts were counted per 100 microns inner circumference of the coronary artery and the numbers observed, i.e. 5.17 +/- 0.50 in fetuses, 1.94 +/- 0.17 in newborns and 0.33 +/- 0.09 in adult animals, proved clearly that the frequency of myo-endothelial contacts, highest in fetuses, decreases with age. With regard to the dual control of the coronary smooth muscle and/or diameter, it is noteworthy that an opposite trend can be observed in the development of innervation of the coronary artery: the autonomic nerve fibres with varicosities are missing in the coronary wall 1 week before birth, while after birth their number keeps increasing. Remarkable enough is also the difference in distances between the endothelium and SMC on the one hand and nerve varicosities and SMC on the other. The above facts indicate a prevalence of endothelial control of coronary diameter.

Aging↗

PubMed1996

Early changes in protein synthesis in epicardial coronary artery of pressure-overloaded heart.

In anesthetized dogs, a 4-h, approximately 30% increase in blood pressure induced by constriction of the abdominal aorta brought about an increase in the total RNA content in the left anterior descending coronary artery (LADCA) and the left ventricular (LV) myocardium (9.05 +/- 1.72 and 11.06 +/- 4.68%, respectively) but not in the left circumflex coronary artery (LCCA). Under the same experimental conditions, [14C]leucine incorporation increased in LADCA and LV myocardium (45.34 +/- 13.54 and 58.07 +/- 11.91%, respectively), but not in LCCA. The data indicate an early shift in protein synthesis in LADCA and simultaneously in the myocardium during a short-term pressor event. The difference in the shift of protein synthesis in the two main branches of the left coronary artery was related to the quantitatively different deformation of the LADCA and LCCA due to different deformation of the underlying myocardium and/or of the annulus fibrosus atrioventricularis during changes in the left or right ventricle volume [M. Gerová, E. Barta, M. Stolárik, and J. Gero, Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H1049-H1053, 1992]. The results support the hypothesis that the deformation and/or rate of deformation of cells in the coronary wall may trigger an increase in protein synthesis. Changes in protein synthesis in the myocardium and LADCA were found to be reversible 2 h after releasing the aortic constriction.

Animals↗

PubMed1996

Nitric oxide in the periendothelial area of femoral vein of the dog assessed in vivo by a porphyrinic sensor.

Nitric oxide concentration in the periendothelial are of the femoral vein in anaesthetized dogs was measured directly with a catheter- protected porphyrinic sensor. A 2- to 4-fold increase occurred in the basal NO concentration of 90 +/- 12 nM after acetylcholine injection (1-1.5 micrograms/kg). A linear correlation was found between femoral artery blood flow and NO concentration in the periendothelial area of the femoral vein. Noradrenaline decreased NO levels below the detection limit of the porphyrinic sensor (10 nM).

Acetylcholine↗

PubMed1996

Vascular responses after long-term inhibition of nitric oxide synthesis in newborn dogs.

The effect of long-term inhibition of nitric oxide synthase on the relaxation and contraction ability of the thoracic aorta, carotid and pulmonary arteries was studied in the early postnatal period. Starting from the fifth day after birth, puppies were administered NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day subcutaneously) for 6 weeks. After this period, mean blood pressure increased from the control value of 94 +/- 14 mm Hg to 168 +/- 5 mm Hg (P < 0.01) and the heart/body weight ratio from 6.22 +/- 0.25 to 8.23 +/- 0.45 (P < 0.01). In control arterial rings precontracted by phenylephrine (10(-5) mol/l), acetylcholine caused dose-dependent relaxations; the maximal values were reached in the range of 10(-8) to 10(-6) mol/l. In arteries from L-NAME treated puppies, acetylcholine also induced dose-dependent relaxations, the maximum values in the thoracic aorta (81.0 +/- 2.9%) and carotid artery (87.2 +/- 6.9%) were significantly reduced, not, however, in the pulmonary artery (76.4 +/- 7.8%). Dose-response curves to acetylcholine in all the examined arteries from L-NAME-treated animals were shifted to the right indicating a decrease in sensitivity to acetylcholine. Neurogenic contractions, induced by electrical stimulation of adrenergic nerves, were not significantly altered in the thoracic aorta and carotid artery. However, in the pulmonary artery the contractions were greater at high frequency of stimulation. The findings that (i) submaximal doses of L-NAME attenuate acetylcholine-induced relaxation only slightly, and (ii) that it does not appreciably influence adrenergic contractions justify the hypothesis that the endothelium of vessels in newborn dogs is very probably endowed with a high content of nitric oxide synthase.

Acetylcholine↗

PubMed1996

Remodelling of septal branch of coronary artery and carotid artery in L-NAME treated rats.

Coronary and carotid artery structure was studied in rats in order to analyze the processes in the cardiovascular system in NO-deficient hypertension model. Long-term inhibition of NO synthase was induced by L-nitro arginine methyl ester (L-NAME, 50 mg/kg/day p.o.) for a period of 8 weeks. An increase in blood pressure and heart/body weight ratio confirmed the reliability of the model. The wall thickness as well as the calculated wall area of the coronary artery increased by 70% and 50%, respectively, in comparison to control vessels. The wall thickness and the calculated wall area of the carotid artery increased by 73% and 70%, respectively. Further analysis indicated that both the tunica intima and tunica media in the coronary and the carotid artery increased quantitatively in a similar manner. Remarkable differences were found in the contribution of cellular and noncellular components in the tunica media of the coronary and carotid arteries of experimental animals. The calculated extracellular area increased by 116% in comparison to the control coronary artery and by 97% in comparison to the control carotid artery. The increase in extracellular matrix of the tunica media of coronary and carotid arteries seems to be basic cause of the remodelling of the vessels studied.

Animals↗