kallidin and Hypertension

1. The kallikrein-kinin system has a significant role in regulating arterial blood pressure. 2. Reduced formation of the kinin compontents may cause hypertensive diseases. This is because of the fact that this system is responsible for vasodilatation, reduction in total peripheral resistance, natriuresis, diuresis, increasing renal blood flow and releasing various vasodilator agents. 3. Reduced kinin-kallikrein generation in hypertensive subjects may also be associated with genetic and environmental defects. 4. The kallikrein-kinin system when administered to hypertensive patients can lower their raised blood pressure to normotensive levels. 5. The mode of action of angiotensin-converting enzyme inhibitors principally may be dependent on the kinin system protection.

Topics: Angiotensin-Converting Enzyme Inhibitors; Base Sequence; Blood Pressure; Humans; Hypertension; Kallidin; Kallikrein-Kinin System; Kininogens; Molecular Sequence Data

Topics: Animals; Arteriosclerosis; Blood Pressure; Bradykinin; Cardiovascular Physiological Phenomena; Coronary Circulation; Coronary Disease; Coronary Vessels; Dogs; Guinea Pigs; Heart; Heart Diseases; Humans; Hypersensitivity; Hypertension; Kallidin; Kinins; Myocarditis; Rheumatic Heart Disease

Topics: Angioedema; Animals; Blood Vessels; Bradykinin; Capillary Permeability; Dilatation; Diuresis; Female; Gout; Humans; Hypertension; Inflammation; Kallidin; Kallikreins; Kinins; Labor, Obstetric; Malignant Carcinoid Syndrome; Muscle, Smooth; Pregnancy; Rats; Salivary Glands; Shock; Synovial Fluid

Topics: Animals; Arteries; Arteriovenous Anastomosis; Blood Circulation; Blood Vessels; Bradykinin; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Coronary Disease; Dogs; Guinea Pigs; Heart; Hemodynamics; Humans; Hypertension; Kallidin; Kallikreins; Kidney; Kinins; Models, Chemical; Myocardial Infarction; Pancreas; Salivary Glands; Shock

Studies in animals and humans indicate a role for kinins in the actions of angiotensin type 1 (AT1) receptor blockers. However, the effect of these compounds on kinin levels in humans is unknown.. We measured angiotensin (Ang), bradykinin (BK), and kallidin peptides in subjects with essential hypertension administered placebo, losartan (50 mg OD), and eprosartan (600 mg OD) in randomized order in a double-blind, 3-period, 3-treatment, crossover trial. Peptides were measured in arterial blood using high-performance liquid chromatography-based radioimmunoassays. Losartan increased blood levels of BK-(1-9) and hydroxylated BK-(1-9) by approximately 2-fold and reduced the BK-(1-7)/BK-(1-9) ratio by 55%. There was a trend for eprosartan to produce similar changes in bradykinin levels. There were no changes in blood kallidin levels. Both losartan and eprosartan increased plasma levels of Ang I, Ang II, and Ang-(2-8), and eprosartan increased Ang-(3-8) levels. Ang-(1-7) and Ang-(1-9) levels were unchanged. There was an associated 30% to 35% reduction in Ang II/Ang I ratio and 63% to 69% reduction in Ang-(1-7)/Ang I ratio. Plasma ACE activity was unchanged.. Losartan increases bradykinin levels. The reductions in BK-(1-7)/BK-(1-9), Ang II/Ang I, and Ang-(1-7)/Ang I ratios suggest that the increased bradykinin levels were the result of reduced metabolism by ACE and neutral endopeptidase. Increased bradykinin levels may represent a class effect of AT1 receptor blockers that contributes to their therapeutic actions and may also contribute to the angioedema that may accompany this therapy.

Topics: Acrylates; Adolescent; Adult; Aged; Angiotensin I; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Bradykinin; Chromatography, High Pressure Liquid; Cross-Over Studies; Double-Blind Method; Female; Humans; Hydroxylation; Hypertension; Imidazoles; Kallidin; Losartan; Male; Middle Aged; Peptide Fragments; Radioimmunoassay; Thiophenes

Interaction between an enhanced action of kinins and cytokines is accepted as important to the cardioprotective effect of angiotensin-converting-enzyme inhibitors. Kinins mediate their effects through B1 and B2 subtype receptors that may be modulated by cytokines including interleukin (IL)-1beta. We examined expression of kinin receptors and the effects of bradykinin (B2 agonist) and des-Arg10-kallidin (B1 agonist) on extracellular matrix components of adult rat cardiac fibroblasts with or without prior exposure to IL-1beta. We compared responses of cells cultured from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) hearts. mRNA levels of kinin receptors, procollagens, promatrix metalloproteinases (proMMP-2 and proMMP-9), and tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2) were all assessed by a semiquantitative RT-PCR. In the absence of IL-1beta, SHR cells expressed more B2 receptor, procollagen alpha1(I), procollagen alpha1(III), and proMMP-9 mRNA than WKY cells. IL-1beta exposure enhanced B1, B2, proMMP-2, and proMMP-9 mRNA in cells of both strains to equivalent levels. Zymographic studies confirmed the results of proMMPs. Following IL-1beta treatment, bradykinin attenuated procollagens alpha1(I) and alpha1(III) mRNA expression in SHR but not WKY cells. In contrast, des-Arg10-kallidin did not show any significant effects in either SHR or WKY cells. Our findings indicate greater extracellular matrix turnover in cultured SHR cardiac fibroblasts than WKY under basal conditions, an IL-1beta stimulation of turnover in cells from both strains, and a strain-differential effect of bradykinin following cytokine treatment. These results imply a genetically determined response of cardiac extracellular matrix and the potential of direct enhancement of the efficacy of kinins by the local release of IL-1beta in hearts genetically programmed to exhibit excessive remodeling to injury.

Topics: Animals; Bradykinin; Cells, Cultured; Collagenases; Drug Synergism; Enzyme Precursors; Extracellular Matrix; Fibroblasts; Gelatinases; Gene Expression; Hypertension; Interleukin-1; Kallidin; Matrix Metalloproteinase 9; Metalloendopeptidases; Myocardium; Procollagen; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Bradykinin B1; Receptor, Bradykinin B2; RNA, Messenger; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

Topics: Angiotensin I; Angiotensin II; Cyclic AMP; Humans; Hypertension; Kallidin; Kallikreins; Kinins; Pressoreceptors; Prostaglandins; Renin

A sensitive and specific radioimmunoassay method for urinary kinins was developed, which uses antiserum against synthetic bradykinin in combination with labeled tyr8-bradykinin. The assay detects as little as 6 pg per tube of bradykinin. The dose-response curves of bradykinin. lysyl-bradykinin (kallidin), and methionyl-lysyl-bradykinin were almost identical. This suggests that the values estimated with bradykinin as the standard exhibit the total urinary kinins which contain these three peptides. The assay was performed without extraction of urinary samples, since a chromatographic study demonstrated that no interfering substances in urine samples remain in our assay system. The urinary levels of total kinins in 10 normal male subjects, three male patients with chronic renal failure, and 12 male patients with essential hypertension was 37.9 +/- 3.9 microgram/day (mean +/- S.E.M.), 9.0 +/- 5.1 microgram/day, and 24.2 +/- 5.2 microgram/day, respectively.

Topics: Adult; Aged; Bradykinin; Glomerulonephritis; Humans; Hypertension; Immune Sera; Iodine Radioisotopes; Kallidin; Kinins; Male; Middle Aged; Radioimmunoassay

Topics: Angiotensin II; Animals; Bradykinin; Depression, Chemical; Dilatation; Female; Goats; Hypertension; Kallidin; Kallikreins; Mammary Glands, Animal; Regional Blood Flow; Thoracic Arteries

Topics: Arthritis; Arthritis, Rheumatoid; Biological Assay; Bradykinin; Chemistry Techniques, Analytical; Eczema; Female; Humans; Hypertension; Kallidin; Kinins; Peptides; Pre-Eclampsia; Pregnancy; Rats; Urine; Uterus

Topics: Bradykinin; Cerebrovascular Disorders; Eledoisin; Humans; Hypertension; Intermittent Claudication; Kallidin; Kinins; Peptides; Trypsin

Topics: Bradykinin; Globulins; Humans; Hypertension; Kallidin; Kallikreins; Vasodilator Agents; Venoms