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)

Biological actions of natriuretic peptide (NP) are determined by the condition of the receptor as well as that of the hormone. Although we previously demonstrated in hypertensive rats the up-regulation of NP-A receptor that mediates various biological actions of NPs, the pathophysiologic significance of NP-C receptor, another subtype thought to be related to clearance of NPs and possibly to biological actions, remains unknown. In the present study, we determined NP-C receptor messenger RNA (mRNA) level in the aortic tissue of stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and in cultured aortic smooth muscle cells by ribonuclease protection assay. The aortic NP-C receptor mRNA level in SHR-SP/Izm was significantly lower than that in the control WKY/Izm. Oral administration of an angiotensin (Ang) II receptor (AT1) antagonist, TCV-116, but not a calcium channel blocker, manidipine, reversed the down-regulated NP-C receptor mRNA in SHR-SP/Izm to the level in WKY/Izm, whereas the latter was more potent in decreasing the blood pressure. In cultured aortic smooth muscle cells, the NP-C receptor was the predominant subtype. Ang II decreased the NP-C receptor mRNA level in a dose-dependent manner, but this effect was reversed by an AT1 antagonist, CV-11974. Neither the NP-A nor NP-B receptor mRNA level was altered by Ang II. These findings indicate that vascular NP-C receptor is down- regulated via Ang-II-mediated mechanism in SHR-SP/Izm. The phenomenon, together with the up-regulation of the NP-A receptor, may play an important role in counteracting hypertension by enhancing the action of NPs.
 ...
PMID:Angiotensin II-dependent down-regulation of vascular natriuretic peptide type C receptor gene expression in hypertensive rats. 860 80

The aim of the present study was to investigate the role of insulin-like growth factor I in the development of cardiac hypertrophy in two-kidney, one clip hypertension by relating growth hormone receptor and insulin-like growth factor I receptor mRNA levels to insulin-like growth factor I gene transcription using a solution hybridization/RNase protection assay. Two-kidney, one clip hypertension was induced in male Wistar rats, and experiments were performed 2, 4, 7, and 12 days after surgery. Systolic blood pressure was elevated 2, 7, and 12 days after clipping (P < .001). Left ventricular weights were increased 2, 4, 7, and 12 days after surgery (P < .01). Associated with the rise in blood pressure, left ventricular insulin-like growth factor I mRNA was increased 2, 7, and 12 days after surgery (P < .01). Furthermore, growth hormone receptor and insulin-like growth factor I receptor gene expression increased specifically in the left ventricle of renal hypertensive rats (P < .05 and P < .001, respectively). Left ventricular growth hormone receptor mRNA peaked 7 days after induction of renal artery stenosis. These results show that insulin-like growth factor I, growth hormone receptor, and insulin-like growth factor I receptor mRNA increase in the pressure-overloaded left ventricle of two-kidney, one clip rats, suggesting a role for insulin-like growth factor I and the growth hormone/insulin-like growth factor I axis in the development of cardiac hypertrophy.
Hypertension 1996 Mar
PMID:Cardiac insulin-like growth factor I and growth hormone receptor expression in renal hypertension. 861 16

Recent studies have shown that all three subtypes of alpha2-adrenergic receptor (alpha2-AR) are found in brain. The purpose of this study was to map the subtype localization of the alpha2A- and alpha2B-ARs in brain structures. RNase protection shows that both the alpha2A- and alpha2B-ARs are detectable in cortex, cerebellum, pons-medulla, and hypothalamus. We tested probes derived from the alpha2A- and alpha2B-AR cDNAs on cell lines that express each of the alpha2-AR subtypes to establish the subtype specificity of these probes for in situ hybridization. Then we used the alpha2A- and alpha2B-AR probes for in situ hybridization on sagittal and coronal sections of rat brain. Both alpha2A and alpha2B mRNA were detected throughout the brain. Overall, there appears to be a greater expression of message for alpha2A- than alpha2B-AR in most brain areas, with the exception of the thalamus. Developing these probes for in situ hybridization is an important step for further studies on the exact role of the alpha2-AR subtypes in neurons that modulate cardiovascular function.
Hypertension 1996 Mar
PMID:Localization of alpha 2A- and alpha 2B-adrenergic receptor subtypes in brain. 869 52

We have developed a transgenic animal model to investigate the effects of overexpression of rat prorenin on the cardiovascular system. Two transgenic rat lines were generated in which rat prorenin expression was directed to the liver by a human alpha1-antitrypsin promoter. Liver-specific expression was confirmed by RNase protection assay. Plasma prorenin concentrations in transgenic rats were increased 400-fold in the males of both lines but were increased only two- to threefold in the females. Thus, transgene expression exhibited sexual dimorphism. Blood pressures were not significantly higher in transgenic rats than in nontransgenic controls. The ratio of heart weight to body weight was greater in male transgenic rats than in the nontransgenic controls. Histological analysis revealed severe renal lesions and hypertrophic cardiomyocytes in transgenic males only. This transgenic model demonstrates a likely role of prorenin in the development of cardiac and renal pathology independent of hypertension. These animals will facilitate studies of the effects of blockade of the renin-angiotensin system and other pharmacological interventions on the development and treatment of cardiac, vascular, and renal lesions induced by changes in this system in the absence of chronic hypertension.
 ...
PMID:Vascular damage without hypertension in transgenic rats expressing prorenin exclusively in the liver. 890 14

Hypertension is commonly associated with diabetes mellitus. The aim of the present study was to explore the pathophysiological significance of the natriuretic peptide (NP) system in hypertension associated with genetically obese/hyperglycemic Wistar fatty rats. The messenger RNA (mRNA) levels of the two biologically active NP receptors, NP-A receptor [more specific for atrial natriuretic peptide (ANP)] and NP-B receptor [more specific for C-type natriuretic peptide (CNP)], and CNP mRNA levels were determined in the aorta and kidney by ribonuclease protection assay. Plasma ANP levels were determined by RIA. Both NP-A and NP-B receptor mRNA levels in the aortae of Wistar fatty rats were double those in Wistar lean rats. Plasma ANP levels and CNP mRNA levels in the aorta of Wistar fatty rats were also significantly higher than those in Wistar lean rats. In contrast, there was no significant difference in renal levels of the mRNA for both NP receptors and CNP between the two strains. Administration of a NP-A and -B receptor antagonist, HS-142-1, to Wistar fatty rats resulted in a significant increase in systolic blood pressure and a larger decrease in plasma cGMP level than that in Wistar lean rats, with no difference in the extents of decrease in urine volume and urinary sodium excretion between the two strains. These results suggest that both the ANP/NP-A system and the CNP/NP-B system in vessels are up-regulated at the level of gene expression and may, thus, play an important role in counteracting the hypertension associated with diabetes mellitus.
 ...
PMID:Vascular action of circulating and local natriuretic peptide systems is potentiated in obese/hyperglycemic and hypertensive rats. 894 Mar 83

We developed a model of spontaneously high human renin hypertension in the rat by producing two transgenic strains, one for human angiotensinogen with the endogenous promoter and one for human renin with the endogenous promoter. Neither transgenic strain was hypertensive. These strains were then crossed, producing a double transgenic strain. The double transgenic rats, both males and females, developed severe hypertension (mean systolic pressure, 200 mm Hg) and died after a mean of 55 days if untreated. The rats had a human plasma renin concentration of 269 +/- 381 (+/-SD) ng angiotensin I (Ang I)/mL per hour, plasma renin activity of 177 +/- 176 ng Ang I/mL per hour, rat angiotensinogen concentration of 1.49 +/- 1 microgram Ang I/mL, and human angiotensinogen concentration of 78 +/- 39 micrograms Ang I/mL (n = 49). Control rats had plasma renin activity of 3.7 +/- 3.9 ng Ang I/mL per hour and rat angiotensinogen of 1.32 +/- 0.16 micrograms Ang I/mL. Angiotensinogen transgene expression by RNase protection assay was ubiquitously present but most prominent in liver. Renin transgene expression was high in kidney but absent in liver. The rats featured severe cardiac hypertrophy, with increased cross section of cardiomyocytes but little myocardial fibrosis. The kidneys showed atrophic tubules, thickened vessel walls, and increased interstitium. Both the angiotensin-converting enzyme inhibitor lisinopril and the specific human renin inhibitor remikiren lowered blood pressure to normal values. Double transgenic mice have been developed that exhibit features quite similar to those described here; their gene expressions are similar. The specificity of rodent and human renin is similarly documented. Although many elegant physiological studies can now be done in mice, rats nevertheless offer flexibility, particularly in terms of detailed cardiac and renal physiology and pharmacology. We conclude that this double transgenic strain will facilitate simultaneous investigation of genetic and pathophysiological aspects of renin-induced hypertension. The fact that human renin can be studied in the rat is a unique feature of this model.
Hypertension 1997 Jan
PMID:High human renin hypertension in transgenic rats. 903 38

1. To elucidate the pathophysiologic role of vascular natriuretic peptide (NP) receptor in hypertension, we determined NP-A and NP-B receptor mRNA levels by means of ribonuclease protection assay in aorta of three types of hypertensive rats. 2. The NP-A receptor mRNA level was higher in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and deoxycorticosterone acetate-salt hypertensive rats than that in their respective control rats. On the contrary, the NP-A receptor mRNA level was lower in NG-nitro-L-arginine-methyl ester (L-NAME)-induced hypertensive rats compared with that in the control. 3. The NP-B receptor mRNA level did not show any significant change in all three hypertensive rats compared with their respective controls. 4. The present study suggests that high blood pressure is not the major factor regulating the NP receptor gene expression and also that the receptor subtype is independently regulated from each other.
 ...
PMID:Gene expression of vascular natriuretic peptide receptor in the aorta of hypertensive rats. 907 44

1. To elucidate the functional implication of very low density lipoprotein (VLDL) receptor, we studied the gene expression of VLDL receptor in rats. The VLDL receptor mRNA was highly expressed in the cardiac ventricle and skeletal muscle. Intermediate amounts of VLDL receptor mRNA were detected in adipose tissue, adrenal gland, brain and lung. Thus the tissue distribution of VLDL receptor mRNA in rats was similar to that reported previously in rabbits. 2. We studied the gene expression of the VLDL receptor in the heart of stroke-prone spontaneously hypertensive rats (SHRSP), an animal model for hypertension-induced cardiac hypertrophy. RNase protection assay showed that the level of ventricular VLDL receptor mRNA was already decreased to one half when hypertension was not fully developed, and further diminished to one fifth when cardiac hypertrophy was established. 3. It is reported that energy utilization in SHRSP hypertrophied myocardium is impaired. Our results suggest that inactive fatty acid metabolism in the ventricle of SHRSP is related to the lowered expression of the VLDL receptor which is postulated as a gate for triglyceride-rich lipoprotein particle.
 ...
PMID:Decreased expression of the very low density lipoprotein receptor mRNA in the cardiac ventricle of spontaneously hypertensive rats. 907 76

We examined the effect of chronic human renin infusion and human renin inhibition on blood pressure in a unique transgenic rat model. We infused incremental doses of human renin (1 to 500 ng/h) with minipumps for 10 days into rats harboring the human angiotensinogen gene [TGR (hAOGEN)1623]. We measured blood pressure and heart rate continuously by telemetry. We found that human renin at 5 ng/h was necessary to increase blood pressure, whereas 10 ng/h caused systolic blood pressure to increase to 215 +/- 13 mm Hg. Heart rate decreased initially but then increased by 100 beats per minute compared with basal values. Drinking behavior also increased. Doses as high as 500 ng/h did not increase blood pressure further. A linear relationship was found between the log of plasma renin activity and systolic blood pressure that increased in slope from days 2 to 9. Rat angiotensinogen levels were low and not influenced by human renin infusion. Human angiotensinogen levels remained stable until 500 ng/h human renin was infused, at which time they decreased by 50% at 9 days. Rat renin gene expression (RNase protection assay) was decreased by human renin infusion, whereas rat and human angiotensinogen gene expressions in liver and kidney as well as angiotensin-converting enzyme gene expression in kidney were not affected. The human renin inhibitor Ro 42-5892 was given by gavage repeatedly to rats receiving human renin at 40 ng/h. Ro 42-5892 lowered blood pressure promptly to basal values. High human renin hypertension in this model is dose dependent, features a steeper relationship between blood pressure and plasma renin activity over time, and is associated with tachycardia and increased drinking. We conclude that the human angiotensinogen transgenic rat offers new perspectives in the study of human renin-induced hypertension.
Hypertension 1997 Apr
PMID:Dose effects of human renin in rats transgenic for human angiotensinogen. 909 95

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


<< Previous 1 2 3 4 5 6 Next >>