Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphometry of cardiomyocytes and capillary domains in the left ventricle myocardium was performed in control rats and in rats treated with nitro-L-arginine methyl ester 50 mg/kg/day p.o. for a period of 8 weeks. The myocardial hypertrophy accompanying the NO-deficient hypertension induced by chronic inhibition of NO synthase is characterized by an increase in thickness of myocardial fibres and by relative rarefaction of the capillary bed, e.g. an alteration in myocardial structure which is typical for pressure overload hypertrophy.
 ...
PMID:Morphometric characteristics of cardiac hypertrophy induced by long-term inhibition of NO synthase. 908 59

Data concerning the effect of NO on the function and structure of the heart are controversial. We have studied two main questions: (i) Does the heart muscle reflect the hypertension induced by long-term inhibition of NO synthase? (ii) Since the arginine-NO pathway is also operative in the autonomic nervous system, the second goal was to ascertain the possible changes of the adrenergic nervous system in the heart after long-term NO synthase inhibition. Wistar rats were administered L-NAME in drinking water (50 mg/kg bw/day) for 8 weeks. Systolic blood pressure and heart rate were monitored weekly. The heart/body weight ratio were determined at the end of experiment. The adrenergic nerve terminals visualized by histochemistry were counted according to Haug's point counting method. Blood pressure increased significantly in L-NAME-treated rats. No changes were found in the heart rate. Heart/body weight ratio increased markedly. Surprisingly, the density of adrenergic nerve terminals did not alter accordingly. The density of adrenergic nerve terminals in the left ventricle and septum decreased but no significant changes were found in the left atrium and the right ventricle. Hypertension due to NO deficiency induced cardiac hypertrophy that was characterized by a decline in the density of adrenergic innervation of the overloaded left ventricle and septum.
 ...
PMID:Long-term inhibition of NO synthase induces cardiac hypertrophy with a decrease in adrenergic innervation. 908 60

The heart weight and the structure of coronary and carotid arteries were studied in NO-deficient hypertension. Wistar rats were administered L-NAME (50 mg/kg/day) in drinking water for a period of 8 weeks. The blood pressure and heart rate were recorded weekly. In one group of control and experimental animals the heart weight was assessed and the heart/body weight ratio (relative heart weight) was calculated. In the other group of control and experimental animals, the cardiovascular system was perfused by a fixative under constant perfusion pressure. The inner circumference and the wall thickness (tunica intima and tunica media) of the coronary (septal branch) and carotid artery were measured using light microscopy and the wall/diameter ratio was calculated. Inhibition of NO synthase induced a significant increase in blood pressure (187.2 +/- 4.2 mm Hg compared to 131.4 +/- 1.9 mm Hg in the controls, p < 0.01). The heart rate decreased (334.4 +/- 7.0 beats/min compared to 352.6 +/- 4.1 beats/min in the controls, p < 0.05). The heart weight increased in NO-deficient rats (1.32 +/- 0.08 g versus 1.10 +/- 0.03 g, p < 0.05); the heart/body weight index increased remarkably (3.09 +/- 0.15 compared to 2.10 +/- 0.04 in the controls, p < 0.01). Morphometry of the septal branch of the left coronary artery indicated a decrease of the inner circumference (664 +/- 24 microns versus 832 +/- 30 microns, p < 0.01), the increased wall thickness (21.15 +/- 0.84 microns compared to 12.47 +/- 0.62 microns in the controls, p < 0.01) and the remarkably changed wall/diameter ratio (1:10 versus 1:21 in the controls). Similar alterations were found in the carotid arteries: the inner circumference was decreased (2456 +/- 39 microns versus 2732 +/- 66 microns, p < 0.01), the wall thickness increased (45.14 +/- 0.41 microns compared to 26.08 +/- 1.23 microns, p < 0.01) and the wall/diameter ratio was changed to 1:17 in comparison with 1:33 in the controls. In conclusion, cardiac hypertrophy and structural alterations of the coronary artery and carotid artery accompany NO-deficient hypertension.
 ...
PMID:Long-term NO synthase inhibition affects heart weight and geometry of coronary and carotid arteries. 908 63

Nitric oxide (NO) has been suggested to play important roles in the pathophysiology of various cardiovascular diseases. This study tested the hypothesis that an attenuated biological action of NO in hypertension is attributed to a change in the gene expression of NO synthase (NOS), a key enzyme involved in NO formation. The expression level of mRNA of endothelial type NOS (NOS-III) was determined in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and Wistar Kyoto rats (WKY/Izm) by ribonuclease protection assay using a partial clone as probe. NOS-III mRNA was expressed ubiquitously in various tissues of WKY/Izm and SHR-SP/Izm either at 5 wk or 13 wk of age. There was no significant difference in the tissue expression of NOS-III mRNA between the two strains at either age. The intensity and localization of the hybridization signal for NOS-III mRNA in the heart of SHR-SP/Izm did not differ from those in the heart of WKY/Izm. These results suggest that the attenuated biological action of NO implied in genetically hypertensive rats is not attributed to an abnormality at the level of NOS-III mRNA expression in the tissues, although lack of an increase in NOS-III gene expression, despite the hypertensive hemodynamic stress, may modify the blood pressure in hypertension.
 ...
PMID:Gene expression of endothelial type isoform of nitric oxide synthase in various tissues of stroke-prone spontaneously hypertensive rats. 910 12

The involvement of nitric oxide (NO) in anxiety was investigated in rats, using the elevated plus maze test. Acute, but not chronic, systemic treatment with N omega-nitro-L-arginine methyl ester (L-NAME, 10 and 60 mg.kg-1), an inhibitor of NO synthase, increased the time spent by the rats in the open arms. Both the acute and chronic treatments with L-NAME inhibited NO synthase in endothelial cells and in the central nervous system, as shown by the increase in mean arterial pressure and decreased NO synthase activity in brain tissue. Chronic treatment with L-NAME also decreased the serum nitrate levels. The anxiolysis induced by acute L-NAME treatment is unlikely to be due to hypertension, since two-kidney one-clip hypertension in non-L-NAME-treated rats failed to significantly change exploratory behaviour in the elevated plus maze. These results indicate that acute inhibition of NO synthesis decreases anxiety in rats.
 ...
PMID:Acute inhibition of nitric oxide synthesis induces anxiolysis in the plus maze test. 910 74

1. Evidence that nitric oxide (NO) bioactivity is altered in chronic hypertension is conflicting, possibly as a result of heterogeneity in both the nature of the dysfunction and in the disease process itself. The brain is particularly vulnerable to the vascular complications of chronic hypertension, and the aim of this study was to assess whether differences in the cerebrovascular responsiveness to the NO synthase (NOS) inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), and to the NO donor 3-morpholinosydnonimine (SIN-1) might indicate one possible source of these complications. 2. Conscious spontaneously hypertensive (SHR) and WKY rats, were treated with L-NAME (30 mg kg-1, i.v.), 7-NI (25 mg kg-1, i.p.), (0.54 or 1.8 mg kg-1 h-1, continuous i.v. infusion) or saline (i.v.), 20 min before the measurement of local cerebral blood flow (LCBF) by the fully quantitative [14C]-iodoantipyrine autoradiographic technique. 3. With the exception of mean arterial blood pressure (MABP), there were no significant differences in physiological parameters between SHR and WKY rats within any of the treatment groups, or between treatment groups. L-NAME treatment increased MABP by 27% in WKY and 18% in SHR groups, whilst 7-NI had no significant effect in either group. Following the lower dose of SIN-1 infusion, MABP was decreased to a similar extent in both groups (around -20%). There was no significant difference in MABP between groups following the higher dose of SIN-1, but this represented a decrease of -41% in SHR and -21% in WKY rats. 4. With the exception of one brain region (nucleus accumbens), there were no significant differences in basal LCBF between WKY and SHR. L-NAME produced similar decreases in LCBF in both groups, ranging between -10 and -40%. The effect of 7-NI upon LCBF was more pronounced in the SHR (ranging from -34 to -57%) compared with the WKY (ranging from -14 to -43%), and in seven out of the thirteen brain areas examined there were significant differences in LCBF. 5. Following the lower dose of SIN-1, in the WKY 8 out of the 13 brain areas examined showed significant increases in blood flow compared to the saline treated animals. In contrast, only 2 brain areas showed significant increases in flow in the SHR. In the rest of the brain areas examined the effects of SIN-1 upon LCBF were less marked than in the WKY. 6. Infusion of the higher dose of SIN-1 resulted in further significant increases in LCBF in the WKY group (ranging between +30% and +74% compared to saline-treated animals), but no significant effects upon LCBF were found in the SHR. As a result, there were significant differences in LCBF between SIN-1-treated WKY and SHR in six brain areas. In most brain areas examined, cerebral blood flow in SHR following the higher dose of SIN-1 was less than that measured with the lower dose of SIN-1. 7. Despite comparable reductions in MABP (approximately 20%) in both groups, calculated cerebrovascular resistance (CVR) confirmed that the vasodilator effects of the lower dose of SIN-1 were significantly more pronounced throughout the brain in the WKY (ranging between -3% and -50%; median = -38%) when compared to the SHR (ranging between -10% and -36%; median = -26%). In the animals treated with the higher dose of SIN-1, CVR changes were broadly similar in both groups (median = -45% in WKY and -42% in SHR), but with the reduction in MABP in SHR being twice that found in WKY, this is in keeping with an attenuated blood flow response to SIN-1 in the SHR. 8. The results of this study indicate that NO-dependent vasodilator capacity is reduced in the cerebrovasculature of SHR. In addition, the equal responsiveness to a non-specific NOS inhibitor but an enhanced effectiveness of a specific neuronal NO inhibitor upon LCBF in the SHR could be consistent with an upregulation of the neuronal NO system.
 ...
PMID:Cerebrovascular effects of nitric oxide manipulation in spontaneously hypertensive rats. 914 86

Several mechanisms are known to participate in cold-induced hypertension, but no information exist on the role of the nitric oxide (NO). In the present study, we assessed the participation of nitric oxide in cold-induced hypertension by means of inhibition of NO synthase. Experiments were performed in rats treated with N omega-nitro-L-arginine (L-NNA) injected i.p. at a dose of 25 mg/kg body weight twice a day for four consecutive days. Control animals received saline injections of the same volume. Two days before the experiment, the femoral artery was cannulated for blood pressure recording. Arterial blood pressure was measured at 25 degrees C for 30 min (control period), followed by a 3.5 hour period at 4 degrees C (cold exposure) and, eventually, a last 3 hour period after removal from cold (back to 25 degrees C). In control animals, at 25 degrees C, mean arterial blood pressure was 112.5+/-3.6 mmHg and heart rate was 380+/-3.5 bpm. L-NNA treatment caused an increase in blood pressure to 155.0+/-3.5 mmHg (P<0.01) and in heart rate to 410+/-6.0 bpm (P<0.05). Exposure to cold caused blood pressure to increase up to 131.5+/-3.6 mmHg (P<0.05) in the control group, whereas no significant change could be measured in treated animals. Recovery from cold exposure led to a decrease in blood pressure in control animals, but not in treated animals. These results indicate that NO plays a role in the development of cold-induced elevation of blood pressure.
 ...
PMID:Participation of the nitric oxide pathway in cold-induced hypertension. 915 97

Nitric oxide (NO) pathway is involved in various physiological and pathophysiological processes. NO is synthesised by NO synthase. Three isoforms, ecNOS, nNOS, iNOS have been identified to date, that are encoded by 3 distinct genes on chromosome 7, 12 and 17 respectively. L-arginine is likely involved in the control of NO synthesis. In the kidney, NO regulates glomerular hemodynamics by modulating the ultrafiltration coefficient and afferent and efferent renal arteriolar resistance. NO is further involved in the pressure-natriuresis mechanism and in the tubuloglomerular feedback. Several physiopathological models have underlined the importance of the NO in arterial hypertension and in glomerular inflammation.
 ...
PMID:[Kidney and nitric oxide]. 918 32

In rats undergoing renal mass reduction (RMR) oral supplementation with the nitric oxide (NO) precursor L-arginine increases glomerular filtration rate and ameliorates signs of glomerular injury, suggesting that chronic renal failure in the rats is a condition of low NO formation in the kidney. On the contrary, data are available that in the systemic circulation of uremics, both rats and human beings, NO is formed in excessive amounts and may contribute to platelet dysfunction and bleeding tendency, well-known complications of uremia. The present study was designed to clarify the pathophysiology of renal and systemic NO synthesis in uremia. We showed that renal ex vivo NO generation, measured as the conversion of [3H] L-arginine to [3H] L-citrulline, was lower than normal in RMR rats, seven days after surgery, and progressively worsened with time in close correlation with signs of renal injury. Consistent with these results, urinary excretion of the stable NO metabolites, NO2-/NO3-, significantly decreased in rats with RMR. To go deeper into the cellular origin and biochemical nature of this abnormality we used two histochemical approaches that could locate either NO synthase (NOS) catalytic activity (NADPH-diaphorase) or NOS isoenzyme expression (immunoperoxidase). NADPH-diaphorase documented a progressive loss of renal NOS activity in RMR rats that co-localized with a strong progressive decrease of inducible NOS isoenzyme (iNOS) immunostaining. At variance with iNOS, endothelial cell NOS (ecNOS) staining was rather comparable in RMR and control kidneys. At variance to the kidney, in the systemic circulation of RMR rats the synthesis of NO increased as reflected by higher than normal plasma NO2-/NO3- concentrations. High systemic NO likely derives from vessels as documented by the increased NOS activity and higher expression of both iNOS and ecNOS in the aorta of RMR rats. Up-regulation of systemic NO synthesis might be an early defense mechanism against hypertension of uremia. On the other hand, more NO available to circulating cells may sustain the bleeding tendency, a well-known complication of uremia.
 ...
PMID:Renal and systemic nitric oxide synthesis in rats with renal mass reduction. 921 60

Pathophysiological effects of nitric oxide (NO)-deficient hypertension are much better known than are the potential morphological changes. Hearts and main arteries were studied in 15 week old male Wistar rats administered NG-nitro-L-arginine methyl ester (L-NAME) for 4 weeks. A does of 40 mg/kg/day increased systolic arterial pressure by 30%, while heart rate decreased by 20%. Heart/body weight ratios were not significantly changed. Total cardiac RNA and DNA content and [14C]leucine incorporation into myocardial protein were, however, increased by 15%, 228% and 97%, respectively. Light microscopy of hearts showed subendocardial areas of necrosis along with different stages of healing. Morphometric evaluation demonstrated significant increase in myocardial fibrosis. Serum lactate dehydrogenase increased by 91%. Proliferation cell nuclear antigen (PCNA) immunohistochemistry indicated positive cells in areas of postischemic repair. Chronic inhibition of NO synthase (NOS) resulted in periarterial fibrosis and hyperplasia of the media in coronary arteries and aorta. RNA and DNA content, and [14C]leucine incorporation into protein of aorta increased by 255%, 95% and 49%, respectively. PCNA staining showed numerous positive nuclei in the media of coronary arteries and the aorta. It is concluded that inhibition of NOS leads to systemic hypertension with focal myocardial fibrosis reflecting reparative responses associated to ischemic injury. This sequence of alterations involves impaired arterial relaxation, and uncontrolled vascular medial proliferation attributed to the absence of smooth muscle cell proliferation inhibition by NO.
 ...
PMID:Chronic inhibition of NO synthesis produces myocardial fibrosis and arterial media hyperplasia. 922 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>