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)

Malignant hypertension developed in an 18-year-old man whose primary hypertension had been diagnosed by chance. Standing blood pressure was 290/170 mmHg. Tests of renal function revealed high blood urea nitrogen and creatinine levels and low levels of both effective renal plasma flow and the glomerular filtration rate. Plasma renin activity and levels of angiotensin II and aldosterone were greatly elevated. Severe concentric left ventricular hypertrophy was noted. The patient received standard antihypertensive treatment with furosemide, propranolol, nifedipine, and prazosin, but his blood pressure did not decrease and there was no improvement in the clinical or biochemical measures. The patient was then given 20 mg of enalapril daily for one year. The inhibition of angiotensin converting enzyme immediately reduced blood pressure. Angiotensin II and aldosterone levels became normal, kidney function and hemodynamics improved, and echocardiograms revealed that the left ventricular hypertrophy had regressed. The results confirm the pathogenetic role of angiotensin II in the development of the malignant phase of hypertension.
 ...
PMID:Treatment of malignant hypertension with an angiotensin converting enzyme inhibitor. 255 Jan 35

To elucidate mechanisms of angiotensin II (Ang II)-related hypertension, we infused angiotensin (76 ng/min s.c.) into rats with minipumps for 10-14 days. Control rats received sham pumps. We measured blood pressure by tail-cuff, and the excretion of aldosterone and prostaglandins (PG) (PGE2, prostacyclin derivative 6kPGF1 alpha, and thromboxane [Tx] derivative TxB2). Angiotensin II increased blood pressure by 20 mm Hg by day 2 and by 90 mm Hg by day 10. Aldosterone excretion increased from 10 to 70 ng/day in Ang II rats by day 7. Urine PGE2 did not increase in angiotensin rats; however, both 6kPGF1 alpha and TxB2 excretion increased with angiotensin. Control rats had no changes in any of these parameters. A sympathetic component was tested in a separate group of angiotensin rats that received phenoxybenzamine (300 micrograms/kg/day) during angiotensin infusion; their increase in blood pressure of 40 mm Hg at 10 days was less than in those rats with angiotensin alone but more than in control rats. Phenoxybenzamine did not influence the angiotensin-induced increases in excretion of 6kPGF1 alpha or TxB2. Additional groups of conscious angiotensin and control rats were equipped with splanchnic nerve electrodes on day 14 for recording of sympathetic nerve activity. Angiotensin rats had greater basal sympathetic nerve activity than the control rats. Incremental methoxamine injections demonstrated altered baroreceptor reflex function in rats receiving angiotensin. We conclude that increased blood pressure with chronic angiotensin infusion is accompanied by increased production of aldosterone and increased sympathetic tone. The latter may be modulated by PG.
Hypertension 1989 Oct
PMID:Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins. 255 21

Angiotensin II (ANG II) and vasopressin (AVP) are two powerful vasoconstrictors, and atrial natriuretic peptide (ANP) is a potent vasorelaxant. The changes in the density or affinity of binding sites for these agents that may alter target organ responsiveness in hypertension are reviewed. ANG II binding in mesenteric arteries was unaltered in one-kidney, one-clip (1-K, 1-C) and in 2-K, 1-C hypertensive rats, while in deoxycorticosterone acetate (DOCA)-salt hypertensive rats ANG II binding to blood vessels was significantly increased. A role of mineralocorticoids to increase the number of vascular ANG II sites in some hypertensive models is suggested. In spontaneously hypertensive rats (SHR) ANG II receptors were increased in young rats in the prehypertensive stage with respect to Wistar-Kyoto (WKY) control rats, but normal in older rats. AVP binding in the vasculature of hypertensive rats was uniformly decreased in inverse correlation to plasma AVP levels, but vascular responsiveness to AVP was exaggerated. Inositol trisphosphate production by blood vessels of SHR in response to AVP showed that increased AVP receptor-coupled phospholipase C activity may mediate in part the exaggerated pressor response in spite of reduced or normal density of receptors for vasoconstrictor peptides. Vascular ANP sites in 2-K, 1-C, 1-K,1-C, and DOCA-salt hypertensive rats varied inversely with plasma concentrations of ANP. Normal densities of ANP receptors in saralasin-sensitive 2-K, 1-C hypertensive rats correlated with ANP sensitivity, while saralasin-insensitive 2-K, 1-C hypertensive rats, which did not respond to ANP, had significantly decreased density of ANP vascular receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Vascular receptors for angiotensin, vasopressin, and atrial natriuretic peptide in experimental hypertension. 255 50

Angiotensin II can stimulate the sympathetic system and inhibit vagal (parasympathetic) outflow under experimental circumstances in animals. Blockade of angiotensin II formation by angiotensin-converting enzyme (ACE) inhibitors might therefore be expected to result in a reduction of sympathetic activity and enhanced parasympathetic activity. Whether this is so in normotensive or hypertensive humans and in human cardiac failure is unclear, since available techniques for recording activity of the sympathetic and parasympathetic systems are imperfect. Nevertheless, most evidence that comes from measurements of venous norepinephrine suggests that the ACE inhibitors have little or no effect on sympathetic activity in normotension and hypertension, although the activated sympathetic system in severe cardiac failure is probably suppressed. It appears that the ACE inhibitors have a parasympathomimetic action that may contribute to the hemodynamic effects of these drugs. Additional information using direct recordings of sympathetic traffic or measurements of norepinephrine "spillover" is needed to clarify the effects of ACE inhibitors on the sympathetic system.
 ...
PMID:Sympathetic nervous system during converting enzyme inhibition. 257 49

1. Angiotensin II (AII) acts as a potent pressor agent directly, by virtue of its vasoconstrictor activity and indirectly, by the volume expansion resulting from stimulation of aldosterone release from the adrenal cortex, leading to sodium and water retention. Various approaches of interfering with the enzymatic cascade leading to the production of AII have been made in an attempt to define therapeutic agents for the control of hypertension and heart failure. 2. AII receptor antagonists, to date, lack oral activity and have a relatively short duration of action, limiting their clinical usefulness. Inhibitors of angiotensin converting enzyme block AII production, are orally active and have been used successfully in the control of hypertension and in the treatment of congestive heart failure. 3. An ideal approach to the blockade of the renin-angiotensin system (RAS) is the inhibition of renin, an enzyme with only one known substrate (angiotensinogen) which catalyzes the first and rate-limiting step in the RAS. Early attempts to discover a renin inhibitor focused on immunologic inhibitors of renin, fragments of the prorenin sequence and compounds related to pepstatin, a potent pentapeptide inhibitor of pepsin and less potent inhibitor of renin. None of these approaches proved feasible for a variety of reasons including poor absorption, short duration of action and weak activity. 4. Substrate analogs offer the greatest promise for clinically useful renin inhibitors. Most recently, synthesis of compounds mimicking the enzyme transition state, the condition of greatest binding affinity, has resulted in renin inhibitors with potencies in the nanomolar range, which have shown hypotensive activity. These compounds contain at least one peptide bond and have limited oral activity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Renin inhibitors: specific modulators of the renin-angiotensin system. 265 8

Hypertension is an important risk factor in the progression of renal failure, particularly in patients with pre-existing glomerulopathies such as diabetes and chronic glomerulonephritis. The mechanisms involved in hypertensive glomerular injury are currently unclear and cannot be studied in humans because of the constraints of human experimentation. However, recent animal studies have elucidated mechanisms which may explain the variable relationship between systemic hypertension and glomerular injury. Experimentally, at similar levels of systemic hypertension, glomerular injury only develops when preglomerular resistances are ineffective, thus allowing the development of glomerular hypertension. The mechanisms by which the haemodynamic stress of elevated intracapillary pressures and flows lead to progressive glomerular damage are at present unknown. Endothelial cell injury, increased mesangial traffic and/or trapping of macromolecules and epithelial cell injury appear to occur early, followed by in situ inflammatory and microthrombotic mechanisms. The intrarenal renin-angiotensin system appears to play an important role in the pathogenesis of progressive glomerular injury. Haemodynamically, angiotensin II (Ang II) has a relatively greater vasoconstrictive effect on efferent than on afferent arterioles. In addition, Ang II decreases the glomerular ultrafiltration coefficient. These combined effects result in increased intraglomerular capillary pressures. Angiotensin II increases the uptake and decreases the egress of circulating macromolecules in the glomerular mesangium and fosters mesangial cell mitogenesis. Thus, inhibition of Ang II generation may explain why angiotensin converting enzyme (ACE) inhibitors may be effective in arresting or slowing the progression of renal failure in experimental animals and in man.
 ...
PMID:Possible mechanism for the renoprotective effect of angiotensin converting enzyme inhibitors. 269 55

Angiotensin II (Ang II) has been shown to cause hypertrophy of cultured quiescent rat aortic smooth muscle cells. This observation along with the recent demonstration of angiotensinogen messenger RNA (mRNA) in the vessel wall has led us to postulate a role for Ang II in hypertensive smooth muscle hypertrophy. One of the earliest responses in a wide variety of cells in response to a growth-promoting agent is the induction of the proto-oncogene c-fos. To investigate the mechanism of the action of Ang II, we investigated the effect of Ang II on the expression of the c-fos gene in rat aortic smooth muscle cells that were made quiescent by being grown in a defined serum-free media for 48 hours. Ang II (10(-6)-10(-10) M) resulted in a dose-dependent increase in c-fos mRNA expression. This induction was angiotensin-receptor specific since it was completely abolished by the competitive inhibitor saralasin. Inhibition of protein synthesis did not block the rise in c-fos mRNA expression; it resulted in a superinduction and stabilization of the c-fos mRNA. Using a nuclear runoff transcription assay, we demonstrated that Ang II stimulated the transcription rate of the c-fos gene. This activation of c-fos gene expression may be an important mechanism in the angiotensin-induced smooth muscle hypertrophy.
Hypertension 1989 Jun
PMID:Angiotensin II induces c-fos expression in smooth muscle via transcriptional control. 273 16

We report a case in which bone metastasis from carcinoma corporis was treated by intra-arterial hypertension chemotherapy. The patient was a 53-year-old female whom we treated by intra-arterial hypertension chemotherapy of CDDP 80 mg and ADM 30 mg with Angiotensin II. Four weeks later she underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy and right common iliac lymph nodes resection. The response of intra-arterial hypertension chemotherapy was charged microscopically. About half (Grade I b) the carcinoma tissue was necrosed.
 ...
PMID:[A case of carcinoma corporis by intra-arterial hypertension chemotherapy]. 278 4

Recently we reported that the contractile agonist angiotensin II induces hypertrophy, not hyperplasia, in cultured rat aortic smooth muscle cells (Geisterfer AAT, Peach MJ, Owens GK: Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 1988;62:749-756). We have further explored the hypothesis that contractile agonists are important regulators of smooth muscle cell growth by examining the effects of another contractile agonist, arginine vasopressin, on growth of cultured rat aortic smooth muscle cells. Autoradiographic analysis as well as cell number determinations showed that arginine vasopressin (1 microM) did not stimulate proliferation in cells made quiescent in a defined serum-free media nor did it augment proliferation in 0.4% fetal bovine serum. However, flow cytometric analysis of cellular protein content demonstrated that arginine vasopressin (1 microM) did induce cellular hypertrophy in quiescent cultures after 4 days of treatment, increasing smooth muscle cell protein content by 35% as compared with vehicle-treated controls. The increase in protein content showed a concentration dependence. Cellular hypertrophy was accompanied by an increase in [35S]methionine incorporation, which was elevated 45% by 24 hours. Both the increase in [35S]methionine incorporation and the increase in protein content could be prevented by the specific arginine vasopressin receptor antagonist. [1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] arginine vasopressin. An increase in [35S]methionine incorporation was observed between 12 and 24 hours after treatment of quiescent smooth muscle cells for only 5 minutes with arginine vasopressin (1 microM). Arginine vasopressin-induced increases in [35S]methionine incorporation was increased within 6 hours after treatment. These studies show that arginine vasopressin, like angiotensin II, induces hypertrophy but not hyperplasia of cultured rat aortic smooth muscle cells.
Hypertension 1989 Oct
PMID:Arginine vasopressin-induced hypertrophy of cultured rat aortic smooth muscle cells. 279 15

Angiotensin II (AII) sensitivity of neurons in the region of the organum vasculosum laminae terminalis (OVLT) was examined electrophysiologically using in vitro hypothalamic brain slices taken from 4-, 9- and 14-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Micropressure application of AII, its competitive antagonist saralasin, and L-glutamate revealed that neurons in this region of SHR were significantly more sensitive to AII than cells in age-matched WKY preparations. Neuronal sensitivity to L-glutamate was similar between SHR and WKY rats at all ages. Following electrophysiological study, hypothalamic and cortical brain slices were assayed for 125I-labelled AII binding. AII receptor binding in the hypothalamic slices from SHR was elevated significantly above binding in WKY hypothalamic slices at 4, 9, and 14 weeks of age. In contrast, AII binding in cortical slices taken from SHR and WKY rats was similar. These data suggest that altered neuronal AII-sensitivity is not a consequence of hypertension development in SHR and may contribute to its development.
 ...
PMID:Development of angiotensin II-sensitive OVLT neurons in SHR and WKY rats. 289 65


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