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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of the brain kallikrein-kinin system in the regulation of arterial blood pressure of normotensive and spontaneously hypertensive rats was evaluated. Intracerebroventricular administration of the kinin antagonist [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin caused no change in mean blood pressure in Wistar-Kyoto, Sprague-Dawley, or spontaneously hypertensive rats. The antagonist proved to be very potent in blocking the pressor effect of intracerebroventricular bradykinin (32 +/- 3 vs. 3 +/- 1 mm Hg, p less than 0.01). It was specific, as the pressor effect induced by other unrelated peptides was similar during the infusion of either vehicle or kinin antagonist (angiotensin II, 25 +/- 4 vs. 26 +/- 2 mm Hg; prostaglandin E2, 48 +/- 3 vs. 47 +/- 8 mm Hg; norepinephrine, 17 +/- 2 vs. 18 +/- 2 mm Hg; leucine-enkephaline, 15 +/- 2 vs. 16 +/- 1 mm Hg; neurotensin, 18 +/- 2 vs. 19 +/- 1 mm Hg; substance P, 19 +/- 2 vs. 19 +/- 2 mm Hg). Intracerebroventricular administration of 1 mg captopril, an inhibitor of kininase II (one of the enzymes responsible for kinin degradation), caused no change in mean blood pressure in normotensive rats, whereas it increased mean blood pressure by 44 +/- 9 mm Hg (p less than 0.01) in spontaneously hypertensive rats. This increase in mean blood pressure was blocked and then reversed into a hypotensive effect (22 +/- 6 mm Hg, p less than 0.05) during the infusion of kinin antagonist. Our data suggest that the pressor effect induced by intracerebroventricular captopril is due to a transient elevation in endogenous brain kinin levels, supporting the hypothesis that the brain kallikrein-kinin system plays a role in the central regulation of blood pressure in spontaneously hypertensive rats.
Hypertension 1990 Apr
PMID:Brain kinins are responsible for the pressor effect of intracerebroventricular captopril in spontaneously hypertensive rats. 218 Aug 19

Overall, there is agreement that the origins of hypertension have a genetic basis. The genetic factors interact with environmental factors that influence expression and intensity of the disorder. As summarized in Table 1, there is evidence from the literature to identify pathways for the development of hypertension in blacks. Organ pathology, characteristic of the clinical phenotypic hypertension, consists of increased peripheral vascular resistance and left ventricular hypertrophy, and, particularly in blacks, nephrosclerosis. In this scheme, an intermediate phenotype is a biochemical or endocrine marker of gene expression that participates in the regulation of blood pressure. Intermediate phenotypic characteristics of essential hypertension include sodium sensitivity, adrenergic activity, cation transport, and endocrine function including renin-angiotensin-aldosterone, kallikrein-kinin, and prostaglandin. Another intermediate phenotype to be included in this discussion is insulin resistance. These intermediate phenotypes of cell and subcellular function are regulated by candidate genes. Alternatively, an intermediate phenotype can be expressed in response to another intermediate phenotype. For example, sodium sensitivity could be mediated by the cation transport mechanism of Na,K-ATPase, or insulin resistance could be induced by an elevated level of adrenergic activity. Gene expression of the intermediate phenotype is also modulated by environmental factors such as dietary sodium, potassium, or calcium, and social stresses or patterns of physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Jun
PMID:Differences in blacks and whites with essential hypertension: biochemistry and endocrine. State of the art lecture. 219 Sep 20

The lack of kinin formation in systemic circulation and in the renal system may lead to the pathogenesis of high blood pressure (hypertension). Angiotensin converting enzyme inhibitors are able to protect the kinin inactivation by kininase II, therefore, causing an accumulation of kinin. Although the concentrations of kinin in plasma after oral administration of ACE inhibitors are conflicting this is mainly due to methodological difficulties. Kinin receptor antagonists are becoming most reliable pharmacological probes for defining the molecular actions of kinin in several physiopathological states, and in the mechanism of actions of drugs which are dependent on the kinin system. The blood pressure lowering effect of ACE inhibitors can be antagonized by the pretreatment with kinin receptor antagonists. I have therefore proposed that the hypotensive action of ACE inhibitors may reflect the activation of kinin receptor. It is suggested that the development of compounds having protective properties on the kallikrein-kinin system might be therapeutically applicable as anti-hypertensive drugs.
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PMID:Does kinin mediate the hypotensive action of angiotensin converting enzyme (ACE) inhibitors? 219 99

Active and inactive kallikrein or a kallikrein-like enzyme are found in the aorta, vena cava, and tail artery and veins of the rat. We studied the concentration of vascular kininogenase in rats with one-kidney, one clip renovascular hypertension and in unilaterally nephrectomized normotensive rats. Six weeks after surgery, active and total vascular kininogenase activity (active plus trypsin-activated) was measured. Blood pressure was 212 +/- 4 mm Hg in the hypertensive rats (n = 33) and 120 +/- 1 mm Hg in the normotensive rats (n = 32) (p less than 0.001). Active kininogenase was lower in the hypertensive rats; although the difference was not significant in the thoracic aorta (56 +/- 8 versus 77 +/- 15), it was highly significant in the abdominal aorta (63 +/- 13 versus 167 +/- 17, p less than 0.001) and tail artery (48 +/- 8 versus 197 +/- 31, p less than 0.003). Total vascular kininogenase activity (active plus trypsin-activated) was lower in the hypertensive rats in all arteries examined: thoracic aorta (183 +/- 16 versus 380 +/- 38, p less than 0.003), abdominal aorta (565 +/- 61 versus 1,093 +/- 74, p less than 0.001), and tail artery (532 +/- 112 versus 1,243 +/- 135, p less than 0.003). Active kininogenase in the vena cava was higher in the hypertensive rats (213 +/- 56 versus 131 +/- 31); however, this difference was not statistically significant, whereas in the tail veins it was highly significant (1,803 +/- 221 versus 771 +/- 79, p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Oct
PMID:A kallikrein-like enzyme in blood vessels of one-kidney, one clip hypertensive rats. 221 Aug 11

A study of 115 patients with rheumatic heart disease associated with arterial hypertension revealed significant changes of functioning of depressor kallikrein-kinin system of the kidneys and blood. The period of formation of arterial hypertension is already distinguished by an exhaustion of the depressor systems manifested in a marked reduction of the kallikrein excretion in response to physical loads and a reduction of the extracellular volume deteriorating in the course of stabilization of arterial hypertension.
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PMID:[The humoral depressor system function in rheumatic heart defects with arterial hypertension]. 227 65

A significant reduction of kallikrein activity in urine (assayed by its amidolytic activity) was found in 64 normotensive workers who had been exposed to cadmium for 11 years on average and whose cadmium concentrations in urine ranged from 2.2 to 33.1 micrograms/g creatinine. The mean (geometric) urinary kallikrein activity (in U/g creatinine) amounted to 0.52 (range 0.11-1.90) in the control group (n = 193) against 0.39 (range 0.10-1.03) in the cadmium group, and the prevalence of abnormally low activity levels (less than or equal to 0.20 U/g creatinine) amounted to 17.2% in the cadmium group against 5.2% in the control group. A reduction of aldosterone release (aldosterone in urine) associated with an increased natriuresis was also observed. This might constitute a compensatory mechanism maintaining blood pressure in the normal range. These biological effects of cadmium were not reversible after removal from exposure. This study indicates that cadmium can induce an irreversible toxic effect in the distal nephron. It also suggests that an excessive cadmium body burden alone may not be sufficient to induce hypertension, but in individuals whose blood pressure regulation may be impaired by other factors cadmium could stimulate the development of hypertension. This study also supports the recommendation to prevent hypertensive subjects from being exposed to cadmium. There was no indication that moderate exposure to mercury vapour (n = 53; mercury in urine, range 11-224 micrograms/g creatinine; average duration of exposure: six years) or to inorganic lead (n = 23; lead in blood, range 40-67 micrograms/100 ml; average duration of exposure: eight years) was associated with a reduction of kallikrein production by the kidney.
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PMID:Urinary kallikrein activity in workers exposed to cadmium, lead, or mercury vapour. 235 54

Over the last three years we have carried out studies on the urine output of both sodium and dopamine in five different ethnic groups: whites, Ghanaians, Zimbabweans, Iranians and Thais. Sodium was measured by ion specific electrode and dopamine by HPLC with electrochemical detection (using epinine as an internal standard). In several groups salt loading studies were also carried out. The five ethnic groups differed substantially with regard to the correlation between their urinary sodium and dopamine outputs. Three groups (whites, Thais and Zimbabweans) showed a strong positive correlation (P less than .001) and this may reflect their traditionally salt rich diet. In two groups (Ghanaians and Iranians) there was no correlation and this may reflect a salt scarce environment. Taken together with our previously reported studies showing that normotensive Ghanaians do not mobilize dopamine on salt loading, this would suggest that certain ethnic groups are predisposed to develop hypertension on salt loading--that is, they are 'salt sensitive.' This genetic trait may have passed from the West Coast of Africa, with the slaves, to America and the Caribbean. Other workers have reported deficiencies in vasodilator systems in the American black, such as dopamine, kallikrein and the renal prostaglandins. These defects may lead to the nosologic entity of 'low renin' hypertension, well described in American blacks, and could open up avenues of therapy based either on DA1 activators (such as fenoldopam) or on renal prodrugs (such as gludopa).
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PMID:Ethnic differences in the renal sodium dopamine relationship. A possible explanation for regional variations in the prevalence of hypertension? 238 74

A study was made of the effects of heparin and sodium fepromaron on prekallikrein (PK); kallikrein inhibitors (KI), initial esterase activity (IEA) of rat blood in health and pituitrin hypertension. Pituitrin hypertension was associated with IEA increase and KI decrease. A single administration of heparin raised IEA; if administered for 3 days, heparin reduced IEA. After pituitrin administration heparin decreased IEA if administered once or for 3 days. Administration of fepromaron in courses following pituitrin also reduced. IEA, with that reduction being preserved for not less than 4 days after drug discontinuation. Similarity of the effects of heparin and fepromaron on hemocoagulation and the tone of blood vessels suggests the common mechanisms of their action on the blood kinin system.
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PMID:[Effect of heparin and fepromaron on the kallikrein-kinin system in pituitrin-induced hypertension]. 241 94

To study the significance of the increased activity of the kallikrein-kinin system described in patients with Bartter's syndrome, we investigated the pressor response to infused angiotensin II in four patients with the syndrome receiving no treatment and during the administration of aprotinin and of indomethacin. Five normal subjects served as controls. Aprotinin is a proteolytic enzyme that inhibits the formation of kinins by inhibiting plasma and glandular kallikrein. Indomethacin, a prostaglandin-synthesis inhibitor, can also inhibit the kallikrein-kinin system and normalizes vascular responsiveness to angiotensin II in Bartter's syndrome. All patients had increased urinary kallikrein and prostaglandin E2 concentrations. Aprotinin significantly decreased the dose of infused angiotensin II required to induce a 20 mm Hg increase in diastolic blood pressure, from 11 +/- 4 ng/kg/min to 7.0 +/- 2.0 ng/kg/min (mean +/- SD; p less than 0.05) in normal subjects and from 135 +/- 57 ng/kg/min to 70 +/- 26 ng/kg/min (p less than 0.05) in the patients with Bartter's syndrome, without significantly changing plasma renin activity, mean control blood pressure, or urinary prostaglandin E2 concentration. Indomethacin normalized the pressor response to angiotensin II in three patients who had been pretreated for 4 days (pressor dose, 10 ng/kg/min) but not in one patient who received a single oral dose of indomethacin 5 hours before the test. Our results suggest that inhibition of the kallikrein-kinin system alone accounts for approximately a 50% decrease in vascular resistance to the pressor effect of angiotensin II in Bartter's syndrome, while additional suppression of prostaglandins entirely normalizes the vascular response to angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Inhibition of the kallikrein-kinin system and vascular reactivity in Bartter's syndrome. 241 84

The influence of aprotinin as a kallidinogenase inactivator on the antihypertensive effect of angiotensin I converting enzyme inhibitor (CEI) was studied in two-kidneyed and one-clipped hypertensive rats. Sixteen two-kidneyed and one-clipped hypertensive rats and sham-operated normotensive rats were prepared for this experiment. They were divided into two groups: those with the aprotinin infusion and those without. The effects of the oral administration of CEI were compared as regards mean arterial pressure (MAP) and urinary kallikrein activity (UKA). In 8 hypertensive rats under glucose infusion, MAP fell from 184.4 +/- 4.5 to 106.3 +/- 5.2 mm Hg, and UKA changed from 1.37 +/- 0.18 nkat/12 h to 0.61 +/- 0.11 nkat/12 h after the administration of CEI. In the remaining hypertensive rats under aprotinin infusion, MAP decreased from 175.0 +/- 3.0 to 140.6 +/- 5.1 mm Hg, and UKA slightly changed from 0.72 +/- 0.25 nkat/12 h to 0.59 +/- 0.12 nkat/12 h. Thus, the decrease of MAP after the administration of CEI was suppressed by the aprotinin infusion, and this significant difference was supported by the decrease of UKA. As for 16 normotensive rats, CEI did not alter MAP, nor did aprotinin have any effect on it. However, UKA tended to decrease after the administration of CEI. These results suggest that both the kallikrein-kinin system and the renin-angiotensin system play an important role in the maintenance of high blood pressure in two-kidneyed and one-clipped chronically hypertensive rats.
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PMID:Role of the kallikrein-kinin system in two-kidneyed and one-clipped hypertensive rats. 243 36


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