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)

The association of arterial hypertension and diabetes mellitus is frequent: one third of patients attending a diabetic clinic. Excess hypertension frequency is marked in type II, non insulin-dependent diabetes, a condition often associated with other vascular risk factors such as obesity and lipid disorders. Insulin resistance is a common feature between type II diabetes, hypertension and other risk factors. In type I, insulin-dependent diabetes, hypertension is often linked to diabetic nephropathy. There is a genetic basis for diabetic nephropathy, which may share a common background with familial hypertension. Apart from possible genetic predispositions to hypertension diabetes association, chronic hyperglycaemia can lead to alteration in functional and structural properties of blood and vessels, which both contribute to elevated vascular resistance and blood pressure. From a therapeutic viewpoint, blood pressure values above 140/90 mmHg are not tolerable in diabetic subjects under 40 years of age. Due to their renal haemodynamic effects, angiotensin I converting enzyme inhibitors may be of special interest to protect kidney function in diabetic subjects.
 ...
PMID:Hypertension and diabetes mellitus. 821 50

In the present experiments the effect of long-term peripheral ischemia on the capillary of two hind limb skeletal muscles was investigated in spontaneously hypertensive rats. Furthermore, the effect of antihypertensive therapy on changes in capillarity and on the previously observed hyperreactivity of the ischemic vascular bed to vasoconstrictors was investigated in perfused hind limbs of rats after long-term treatment with the angiotensin I converting enzyme inhibitors captopril (0.5 mg/kg.h) or zabiciprilate (0.025 mg/kg.h), the angiotensin II type 1 receptor antagonist losartan (0.625 mg/kg.h), or the calcium antagonist felodipine (0.042 or 0.42 mg/kg.h). Skeletal muscle ischemia in the left hind limb was induced by partial ligation of the left common iliac artery. Long-term (4 weeks) ischemia increased significantly the capillary-to-fiber ratio in the soleus muscle, composed predominantly of type I fibers in spontaneously hypertensive rats, of the ischemic hind limb, whereas capillarity in the contralateral muscle was not affected. Furthermore, capillarity in the gastrocnemius muscle (type II muscle fiber part) of both the ischemic and contralateral hind limb did not change. Long-term treatment with the angiotensin I converting enzyme inhibitors during ischemia abolished the increase in the capillary-to-fiber ratio in the soleus muscle, whereas a comparable antihypertensive dose of felodipine had no effect. Greater blood pressure reductions by both losartan and felodipine prevented increases in capillarization in skeletal muscle ischemia. With respect to vascular hyperreactivity during ischemia, only treatment with losartan normalized reactivity of the ischemic vascular bed to vasoconstrictors.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Nov
PMID:Antihypertensive therapy and adaptive mechanisms in peripheral ischemia. 822 38

To study the oxytocic effect of trypsin, we measured the force of isometric contraction in uteri isolated from estrogenized rats exposed to trypsin (8.8 x 10(-10) to 1.7 x 10(-6) mol/L) either alone or in the presence of receptor antagonists to angiotensin II [saralasin ([Sar1,Ala8]angiotensin II) or DuP 753 (losartan)] or to kinins (D-[Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin). We found that saralasin or DuP 753, but not the kinin antagonist, displaced the dose-response curve to the right. Exposure to exogenous angiotensin I desensitized the preparation to further doses of either angiotensin I or II or trypsin, without altering the effects of oxytocin or bradykinin. Enalaprilat (an angiotensin I converting enzyme inhibitor) or pepstatin A (a renin inhibitor) also displaced the dose-response curve to trypsin to the right, without altering the effects of oxytocin or angiotensin II. Our results indicate that the response to trypsin is mediated by an agent produced from a substrate present in the uterus and acting on the angiotensin II type 1 receptor and are consistent with both renin and angiotensin I converting enzyme being involved in its mechanism of action, thus supporting the notions that the renin-angiotensin system may be important in the late stages of pregnancy and that serine proteases existing in the uterus may contribute to its activation.
Hypertension 1994 Jan
PMID:Oxytocic effect of trypsin on the isolated rat uterus. 828 69

Phenotypic abnormalities of the renin-angiotensin system have been associated with the predisposition to high blood pressure. The angiotensin I converting enzyme (ACE) gene has been implicated as a candidate gene. We examined the distribution of common alleles of the ACE gene and measured circulating components of the renin-angiotensin system and urinary sodium excretion in 170 young Caucasian adults with contrasting genetic predisposition to high blood pressure. Predisposition was defined on the basis of personal and parental blood pressure levels by using the four corners sampling method. Young adults with greatest predisposition who had high blood pressure and two parents with high blood pressure did not show any significant difference in the distribution of the markers of the ACE gene, either as genotype or allele frequencies, when compared with young adults with least predisposition who had low blood pressure and two parents with low blood pressure. Offspring with urinary sodium excretion above the median (143.4 mmol per day) also showed no significant differences in the distribution of ACE alleles or genotype between groups. Different genotypes were associated with different average serum ACE concentrations (p < 0.0001), but plasma angiotensin II and aldosterone showed no significant variation with ACE genotype. These results suggest that in a group of Caucasians selected from the general population, the ACE gene is not associated with genetic predisposition to high blood pressure. In this population common ACE gene allelic markers would not be useful indexes of susceptibility to hypertension.
Hypertension 1993 Apr
PMID:The angiotensin I converting enzyme gene and predisposition to high blood pressure. 838 2

Incubation with captopril, an angiotensin I converting enzyme inhibitor, for 24 hours at concentrations up to 10(-7) M inhibited endothelin-1 secretion by endothelial cells. This inhibition of endothelin-1 secretion was reversed by coincubation with 3 x 10(-3) M NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis. Furthermore, captopril enhanced the production of nitric oxide in endothelial cells, suggesting that enhancement of nitric oxide production participates in captopril-induced inhibition of endothelin-1 secretion. Moreover, in the presence of 10(-6) M D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin, a bradykinin B2 receptor antagonist, captopril did not inhibit but rather stimulated endothelin-1 secretion, whereas bradykinin inhibited endothelin-1 secretion, and this inhibition by bradykinin was reversed by coincubation with NG-nitro-L-arginine. In addition, enhancement of nitric oxide production induced by either captopril or bradykinin was inhibited by D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin. Although 10(-6) M des-Arg9-[Leu8]-bradykinin, a bradykinin B1 receptor antagonist, did not affect nitric oxide production by bradykinin, it enhanced the inhibition of endothelin-1 secretion by bradykinin. Furthermore, 10(-7) M des-Arg9-bradykinin, a bradykinin B1 receptor agonist, stimulated endothelin-1 secretion by endothelial cells. These findings suggest that angiotensin I converting enzyme inhibitor inhibits endothelin-1 secretion by the accumulation of endogenous bradykinin in endothelial cells and that the inhibition of endothelin-1 secretion by bradykinin is mediated via B2 receptors.
Hypertension 1993 Jun
PMID:Captopril inhibits endothelin-1 secretion from endothelial cells through bradykinin. 838 25

Hypertension is known to place the individual with IDDM at high risk for the development of both renal and cardiovascular disease. Recent data suggest that aggressive antihypertensive therapy (angiotensin I converting enzyme inhibitors, prazosin, and calcium channel blockers) have significantly improved overall prognosis and long-term survival for individuals with IDDM. Because in individuals with IDDM the development of both hypertension and renal disease has its roots in childhood, it is important that early and effective antihypertensive treatment begin there.
 ...
PMID:Hypertension in individuals with insulin-dependent diabetes mellitus. 841 12

Since the renin angiotensin system (RAS) is established as an important factor in renal disease progression, we determined whether RAS alleles that have been linked to variability in outcome in several cardiovascular diseases also affect progression of IgA nephropathy. These genetic variants include: (1) angiotensin I converting enzyme deletion polymorphism in intron 16 (ACE I/D), reported to be associated with increased risk of myocardial infarction as well as left ventricular hypertrophy; (2) a point mutation in the angiotensinogen (Agt) gene resulting in a methionine to threonine substitution at residue 235 (M235T), reported to be associated with hypertension in Caucasians; and (3) an angiotensin receptor type I (ATR) A to C transition at bp 1166 (A1166C) which shows synergy with the deleterious effects of the ACE DD genotype in myocardial infarction. We examined these polymorphisms by PCR amplification of genomic DNA samples from 64 Caucasian patients in the USA (age 6 to 83 years) with biopsy-proven IgA nephropathy whose renal status was followed for an average of almost seven years. Patients who presented with and maintained normal serum creatinine (Cr, < 1.5 mg/dl), had ACE genotype frequencies of II:35%, ID:61%, DD:4%. By contrast, in patients with progression (initially normal Cr increased to a mean of 4.5 +/- 0.86 mg/dl), ACE genotype frequencies were II:22%, ID:44%, DD:33% (P = 0.057 by Fishers's exact test, vs. non-progressors). The association of the DD genotype with progression was even more striking when patients with other risk factors (hypertension and/or heavy proteinuria) were excluded. In this subgroup, the genotype frequencies in patients with stable creatinine versus those with deterioration in renal function was 53%, 47%, and 0% versus 0%, 40%, and 60%, respectively, for II, ID, and DD genotypes (P = 0.009 by Fisher's exact test, progressors vs. non-progressors). Further, sequence analysis of the I gene polymorphism revealed a potential 13 bp silence motif. Neither the Agt 235T nor the ATR A 1166C gene variants, however, was associated with deterioration of renal function. Taken together, these results indicate that, although polymorphism in each of the three genes in the RAS system has been linked to cardiovascular diseases, only the ACE I/D polymorphism is associated with progressive deterioration in renal function in IgA nephropathy. Since previous observations link ACE polymorphism with ACE activity, these findings imply a widespread importance of ACE in modulating destructive processes in different organs.
 ...
PMID:Angiotensin converting enzyme gene polymorphism: potential silencer motif and impact on progression in IgA nephropathy. 882 46

Hypertension is a polygenic disease of world-wide concern. So far, no polygenic disease has been solved at the genetic level. Ethnic differences in the prevalence of hypertension may suggest candidate genes worthy of study. A strong genetic predisposition to hypertension and target organ damage appears to correlate with African ancestry, referred to as "the African gene." Sub-Saharan Africans have endured the selective pressure of extreme heat for thousands of generations. Polymorphisms in the renin-angiotensin system, such as the recently described insertion/deletion polymorphism in the angiotensin I converting enzyme (ACE) gene, may predispose to hypertension and related disorders because of an advantage they confer in thermoregulation.
 ...
PMID:Hypertension, thermotolerance, and the "African gene": an hypothesis. 882 30

The present study was undertaken to investigate whether the development of proteinuria in the borderline hypertensive rat (BHR) is influenced by the Y chromosome and to determine if the onset of proteinuria in the BHR is delayed when blood pressure is lowered with enalapril, an angiotensin I converting enzyme inhibitor. Male F1, rats were the first-generation offspring of the mating of spontaneously hypertensive (SHR) females and Wistar-Kyoto (WKY) males and the mating of SHR males and WKY females. At 20 weeks of age, enalapril (125 mg/l) was added to the drinking water. Untreated BHR and enalapril-treated BHR (BHRE) were followed to 90-100 weeks of age. Urine was collected every 10-20 weeks for determination of protein, albumin, and nitric oxide (NO2/NO3) metabolite excretion. Indirect blood pressure in BHR from both crosses was approximately 175 mm Hg from 20 to 90-100 weeks of age. Enalapril lowered blood pressure by about 30 mm Hg, but was ineffective in reducing urinary protein or albumin excretion rates at any age. Urinary excretion of nitric oxide metabolites was similar in all groups at all time periods. There were significant differences in the percent of glomerulosclerosis between the two matings. Based on these results, renal injury in the BHR is not associated with the Y chromosome and can be dissociated from hypertension. Further studies using congenic and transgenic technology will be necessary to identify functions of genes and associations with hypertension in order to understand the kidney disease in this model of hypertension.
 ...
PMID:Sex chromosomes do not influence renal injury in borderline hypertensive rats. 885 66

Diabetic nephropathy is a glomerular disease due to uncontrolled diabetes and genetic factors. It can be caused by glomerular hypertension produced by capillary vasodilation, due to diabetes, against constitutional glomerular resistance. As angiotensin II increases glomerular pressure, we studied the relationship between genetic polymorphisms in the renin-angiotensin system-angiotensin I converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II, subtype 1, receptor-and the renal involvement of insulin-dependent diabetic subjects with proliferative retinopathy: those exposed to the risk of nephropathy due to diabetes. Of 494 subjects recruited in 17 centers in France and Belgium (GENEDIAB Study), 157 (32%) had no nephropathy, 104 (21%) incipient (microalbuminuria), 126 (25 %) established (proteinuria), and 107 (22%) advanced (plasma creatinine > or = 150 micromol/liter or renal replacement therapy) nephropathy. The severity of renal involvement was associated with ACE insertion/deletion (I/D) polymorphism: chi2 for trend 5.135, P = 0.023; adjusted odds ratio attributable to the D allele 1.889 (95% CI 1.209-2.952, P = 0.0052). Renal involvement was not directly linked to other polymorphisms. However, ACE I-D and AGT M235T polymorphisms interacted significantly (P = 0.0166): in subjects with ACE ID and DD genotypes, renal involvement increased from the AGT MM to TT genotypes. Thus, genetic determinants that affect renal angiotensin II and kinin productions are risk factors for the progression of glomerular disease in uncontrolled insulin-dependent diabetic patients.
 ...
PMID:Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group. 912 2


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