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Biomedical subjects

Thomas Unger

Publications and source records attributed to Thomas Unger.

At least 55 records · Page 3Linked to original sources
PubMed2004

HYDRA: possible determinants of unsatisfactory hypertension control in German primary care patients.

The Hypertension and Diabetes Screening and Awareness (HYDRA) study is a cross-sectional point-prevalence study performed in September 2001; 45,125 primary care attendees were recruited from a representative nationwide sample of 1912 primary care practices in Germany. Around 42% of all patients presenting in these practices had hypertension (WHO definition). In approximately 70% of these patients, hypertension was diagnosed by doctors and 84% of diagnosed patients were on antihypertensive medication, but in less than 30% of treated patients was blood pressure controlled (< 140/90 mmHg). The control rate in all patients presenting with hypertension (including those patients unrecognized) was as low as 19%. The present analysis aimed to find explanations for this unsatisfactory outcome of hypertension control. The main finding was that the rate of diagnosis of hypertension is alarmingly low in young people, probably due to insufficient blood pressure screenings. The data further indicated that doctors still set their target of treatment according to outdated guidelines and that doctors still orientate their treatment primarily with regard to the diastolic pressure. These insights into the causes of unsatisfactory hypertension control may help to direct future educational programmes designed to improve hypertension management specifically to these deficits and thereby to improve control rates.

Adolescent↗
PubMed2004

High prevalence and poor control of hypertension in primary care: cross-sectional study.

OBJECTIVE: To report: (1) on the background, design and methods of the Hypertension and Diabetes Risk Screening and Awareness (HYDRA) study, (2) on the point prevalence of hypertension in primary care and (3) on the proportion of treated, controlled, and uncontrolled hypertension. DESIGN: Cross-sectional point prevalence study. SETTING: Representative nationwide sample of 1912 primary care practices in Germany. PARTICIPANTS: A total of 45,125 unselected primary care attendees. MAIN OUTCOME MEASURES: Prevalence of hypertension based on doctor's diagnosis, self-reported diagnosis, and blood pressure (BP) measurements. RESULTS: A total of 39% of all patients and 67% of patients aged 60 years or older, respectively, were diagnosed by their doctors as having hypertension. Eighty-four percent of diagnosed patients were on antihypertensive medication, 57% of which were rated by the physician as well controlled. When hypertension was defined as either current BP levels > or = 140/90 mmHg and/or current antihypertensive medication, the total point prevalence increased to 50%, while treatment and control rates (BP < 140/90 mmHg) dropped to 64 and 19%, respectively. CONCLUSIONS: Extrapolation of these findings to the entire primary care patient population seen in the over 20 000 primary care practices in Germany suggests that on an average day, over 700,000 patients with elevated BP are seen by primary care physicians, but that only around 132,000 of these patients are well controlled. Thus, this study not only documents the enormous burden of hypertensive patients in the primary health system, but also highlights the alarming lack of BP control in the vast majority of hypertensive patients.

Adolescent↗
PubMed2004

Challenges in improving prognosis and therapy: the Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial programme.

Hypertension is one of the most important modifiable risk factors for cardiovascular pathology, such as atherosclerosis and cardiac left ventricular hypertrophy, including acute events such as stroke and myocardial infarction (MI). In particular, the risk of ischaemic and haemorrhagic stroke is directly and continuously related to high blood pressure levels. The renin-angiotensin system (RAS) plays an important role in volume homeostasis and blood pressure regulation. It also helps to prevent cell and organ damage from ischaemia during acute volume loss. However, angiotensin-II (A-II)--the main effector peptide of the RAS--also exerts a number of pathological effects, which are mediated by the AT 1 receptor. The Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial (ONTARGET) programme consists of two parallel trials where ONTARGET as a large, long-term study compares the efficacy of the angiotensin-receptor antagonist, telmisartan, the renin-angiotensin-converting enzyme (ACE) inhibitor, ramipril and combination therapy with telmisartan plus ramipril for reducing cardiovascular and cerebral risk. Telmisartan, due to its long duration of action, compares favourably with other angiotensin-receptor antagonists. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril was shown to reduce the risk for MI and other cardiovascular events in patients at high risk for pathological cardiac events, but without heart failure or a low ejection fraction. The cardiovascular outcomes of high-risk patients using the same criteria as those of the HOPE study will be assessed in both trials. TRANSCEND differs from ONTARGET in that this trial will enrol patients who do not tolerate ACE inhibitors. This parallel study will therefore be able to compare telmisartan and placebo treatment. Both ONTARGET and TRANSCEND trials feature the same primary composite end point: death caused by cardiovascular disease, acute MI, stroke and hospitalisation because of congestive heart failure. The secondary end points will focus on reductions in the development of Type 2 diabetes mellitus, nephropathy, cognitive decrease and dementia as well as atrial fibrillation.

Angiotensin II↗
PubMed2004

The role of olmesartan medoxomil in the management of hypertension.

Intensive blood pressure control is a desirable and obtainable goal in patients with hypertension, according to the most recent treatment guidelines from Europe and the US. Achieving target blood pressure depends on the efficacy of antihypertensive treatment and patient compliance. Olmesartan medoxomil, a non-peptidergic angiotensin AT1 receptor antagonist, has been shown to be effective and well tolerated. Continuation of initial treatment is higher with AT1 receptor antagonists than for any other class of antihypertensive drugs. Olmesartan medoxomil may also have end-organ protective effects that provide additional clinical benefit. Optimal blood pressure control may be achieved faster if initial treatment contains the most efficacious and well tolerated antihypertensive drug or drugs. The ongoing European study, known as OLMEBEST (Efficacy and safety of OLMEsartan: reduction of Blood pressure in the treatment of patients suffering from mild to moderate ESsenTial hypertension), will provide important information on the use of olmesartan medoxomil as an initial treatment for hypertension.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

The role of the renin-angiotensin-aldosterone system in heart failure.

Activity of the renin-angiotensin-aldosterone system (RAAS) is increased in patients with heart failure, and its maladaptive mechanisms may lead to adverse effects such as cardiac remodelling and sympathetic activation. Elevated renin activity has been demonstrated in patients with dilated cardiomyopathy. (Third- generation synthetic non-peptide renin inhibitors, with more favourable properties than earlier renin inhibitors, lower ambulatory blood pressure and may have a role to play in other cardiovascular disease.) Chymase, a protease inhibitor stored in mast cells that generates angiotensin II (Ang II) (in addition to angiotensin-converting enzyme [ACE]), has been linked to extracellular matrix remodelling in heart failure. Again, chymase inhibitors have been developed to investigate its functions in vitro and in vivo . Bradykinin is thought to contribute to the cardioprotective effect of ACE inhibition through modification of nitric oxide release, calcium handling and collagen accumulation. Ang II is believed to influence a number of molecular and structural changes in the heart, mostly mediated through the AT1-receptor. The importance of the RAAS in heart failure is shown by the survival benefit conferred by treatment with ACE inhibitors.

Aldosterone↗
PubMed2004

Vasoactive peptides, their receptors and drug development.

Vasoactive peptides with vasoconstrictor properties play an important role in many physiological and pathological conditions. The peptides act via specific receptors, most of them belonging to the group of seven transmembrane G-protein coupled receptors. These receptors have become important targets for drugs developed to inhibit vasoconstrictor actions. Alternatively, compounds which inhibit enzymes generating vasoactive peptides have also been demonstrated to represent valuable therapeutic tools. This review will first describe the properties and distribution of two very potent vasoconstrictors, angiotensin II and endothelin. It will further focus on their receptors and on new drugs, which act as antagonists for these receptors. In addition, the properties of indirectly acting drugs like angiotensin-converting enzyme inhibitors and--in analogy--endothelin-converting enzyme inhibitors will be presented.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Comparison of cardioprotective effects of mibefradil and ramipril in stroke-prone spontaneously hypertensive rats.

AIM: To elucidate the cardioprotective effects of T-type calcium channel blocker mibefradil and compare with that of the angiotensin-converting enzyme inhibitor ramipril in a stroke-prone spontaneously hypertensive rats (SHR-SP) model of congestive heart failure (CHF) after myocardial infarction (MI). METHODS: SHR-SP rats were subjected to permanent ligation of the left anterior decending coronary artery. Treatment with mibefradil (10 mg.kg(-1).d(-1)), ramipril (10 mg.kg(-1).d(-1)), or placebo was initiated 4 weeks before surgery and continued up to 6 weeks after induction of MI. Sham-operated rats served as controls. RESULTS: In placebo-treated MI rats, six weeks after MI, left ventricular circumference, inner diameter, and left ventricular end-diastolic pressure (LVEDP) were increased, whereas mean arterial blood pressure (MAP) and maximum rate of rise of left ventricular pressure (dp/dt(max)) were decreased compared with sham-operated controls (P<0.01). In ramipril-treated MI rats, heart weight, heart weight to body weight ratio and interstitial collagen content were reduced (P<0.05, P<0.01), LVEDP was slightly decreased (P>0.05), and dp/dt(max) was improved (P<0.01) compared with placebo-treated MI rats. In contrast, in mibefradil-treated MI rats, heart weight, heart weight to body weight ratio were slightly but not significantly reduced, LVEDP was slightly elevated compared with placebo-treated MI rats, and was elevated (P<0.05) compared with ramipril-treated MI rats, although interstitial collagen content were reduced (P<0.01) compared with placebo-treated MI rats. CONCLUSION: Chronic treatment with ramipril diminishes cardiac remodeling of heart failure after MI to a greater extent than mibefradil. Moreover, 6 weeks after MI, mibefradil treatment results in a slight rise in LVEDP compared with placebo-treated rats. Therefore, treatment with mibefradil might be deleterious rather than beneficial compared with ramipril or even placebo treatment in experimental MI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Angiotensin II AT(1)-receptor induces biglycan in neonatal cardiac fibroblasts via autocrine release of TGFbeta in vitro.

OBJECTIVE: After myocardial infarction, angiotensin II (AngII) promotes ventricular remodeling and deposition of extracellular matrix (ECM), e.g., collagen type 1 and 3. Whether AngII regulates the expression of small leucine-rich proteoglycans (SLRP) which are important modulators of collagen fibrillogenesis and are induced after experimental myocardial infarction in rats is not known. The aim of the present study was therefore to analyse in cultured cardiac fibroblasts the expression and secretion of the SLRP biglycan in response to AngII. METHODS: Cardiac fibroblasts were isolated from neonatal Wistar Kyoto rats and used in the first passage. Expression of AT(1)- and AT(2)-receptors was verified by RT-PCR. Expression of protoeglycans was analyzed after metabolic labeling with [35S]-sulfate, by SDS-PAGE and Western analysis. In addition, mRNA expression was examined by means of RT-PCR and Northern analysis. The activity of the biglycan promoter was analyzed using three biglycan promoter-luciferase fusion constructs. RESULTS: Biglycan was found to be the predominant proteoglycan produced by neonatal cardiac fibroblasts in vitro. In response to AngII (10(-7) M), secretion of total [35S]-labeled proteoglycans and mRNA of biglycan were increased to 116+/-1.8% and 121+/-11% (n=5, mean+/-S.E.M.) of unstimulated controls, respectively. Biglycan induction in response to AngII was sensitive to Losartan (10(-5) M) and unaffected by PD123177 (10(-6) M), suggesting that the AT(1)-receptor mediates the induction of biglycan. Direct activation of the biglycan promoter downstream of the AT(1)-receptor was excluded by promoter activity assays. Instead, increased release of transforming growth factor beta 1 (TGFbeta1) was detected by ELISA in response to AT(1)-receptor stimulation. Furthermore, neutralising antibodies to TGFbeta1 inhibited biglycan induction in response to AngII. CONCLUSION: The results indicate that in cardiac fibroblasts AngII via the AT(1)-receptor causes autocrine release of TGFbeta1, which in turn induces biglycan expression and secretion.

Angiotensin II↗
PubMed2003

Angiotensin II accelerates functional recovery in the rat sciatic nerve in vivo: role of the AT2 receptor and the transcription factor NF-kappaB.

The AT2 receptor regulates several functions of nerve cells, e.g., ionic fluxes, cell differentiation, and axonal regeneration, but also modulates programmed cell death. We tested the hypothesis that angiotensin II (ANG II) via its AT2 receptor not only promotes regeneration but also functional recovery after sciatic nerve crush in adult rats. ANG II (10(-7), 10(-9), 10(-11) M) applied locally via osmotic minipumps promoted functional recovery with maximal effects after the lowest concentration. The toe spread distance as a parameter for re-innervation after 20 days was significantly (P<0.01) greater (10.2+/-10.27 mm) compared with the control group (8.73+/-0.16 mm). The response to local electrical stimulation (return of sensorimotor function) was reduced to 14.6 days vs. 17.9 days in the control group (P<0.01). The AT2 receptor antagonist PD 123319 administered alone or in combination with ANG II completely prevented the ANG II-induced recovery, whereas the AT1 receptor antagonist losartan had no effect. Furthermore, ANG II induces, via the AT2 receptor, activation of the transcription factor NF-kappaB in Schwann cells. Histological criteria, morphometric analyses, and electron microscopy confirmed the functional data. These results are the first to present direct evidence for an involvement of the AT2 receptor and NF-kappaB in peripheral nerve regeneration.

Angiotensin II↗
PubMed2003

p38 MAP kinase negatively regulates angiotensin II-mediated effects on cell cycle molecules in human coronary smooth muscle cells.

Many of the signaling events in VSMC stimulated by angiotensin II (AngII) are mediated by members of the mitogen-activated protein kinase (MAPK) family, including p38 MAPK. The role of p38 MAPK in AngII-mediated cell cycle regulation is poorly understood. Therefore, we examined the involvement of p38 MAPK signaling in AngII-stimulated DNA synthesis, phosphorylation of the retinoblastoma protein (Rb), and expression of the G1-phase cyclin D1 in human coronary artery smooth muscle cells (CASMC). AngII (1 microM) stimulated p38 MAPK and ERK1/2 activation. Pretreatment with the p38 MAPK inhibitors SB203580 (10 microM) (SB) or SKF-86002 (10 microM) (SKF) potently inhibited AngII-induced p38 MAPK activation, but enhanced AngII-mediated ERK1/2 activation. AngII-induced-phosphorylation of Rb (Ser 795 and Ser 807/811), -cyclin D1 expression, and -DNA synthesis was also markedly enhanced by pharmacological inhibition of the p38 MAPK pathway. The present study demonstrates that p38 MAPK negatively regulates AngII-induced ERK1/2 activity, Rb phosphorylation, cyclin D1 expression, and DNA-synthesis in human CASMC. These findings support an important role for p38 MAPK in modulating AngII-mediated VSMC hyperplasia.

Angiotensin II↗
PubMed2003

Pathophysiological activity in rat dorsal horn neurones in segments rostral to a chronic spinal cord injury.

As a sequel of complete spinal cord injury (SCI), patients often develop chronic pain which is perceived at or just below the level of the lesion. Likewise, in animal models of SCI, spontaneous and evoked pain-related behaviour can be observed. In the present study, the hypothesis was tested that pain related behaviour after SCI in animals is at least partly due to neuronal hyperactivity in spinal segments rostral to the site of injury. In rats with a chronic transected spinal cord, the impulse activity of single dorsal horn neurones was recorded in two locations: (1) directly rostrally adjacent to the lesion, and (2) 2-3 segments more rostrally. Cord transections were made either at the thoracic or at the lumbar level. Sham-operated rats and rats which underwent no surgical interventions served as controls. Compared with both controls, in SCI animals the background activity of the neurones had a significantly higher level in both series. Often the activity showed a pathophysiological altered discharge pattern. Following SCI, there was a general increase in the mechanical responsiveness of neurones that were recorded 2-3 segments rostrally to the lesion. The results suggest that neuronal hyperactivity in spinal segments just rostral to the lesion may contribute to chronic spontaneous SCI pain. Further, there is some indication that the allodynia perceived in body regions near and above the level of the SCI may be due to increased responsiveness to weak stimuli of neurones located more rostrally to the lesion.

Animals↗
PubMed2003

The ongoing telmisartan alone and in combination with ramipril global endpoint trial program.

The renin-angiotensin system evolved to maintain volume homeostasis and blood pressure and to prevent ischemia during acute volume loss. But in the present age, these mechanisms are redundant, and the clinical significance of angiotensin II results from its pathologic effects, which are mediated by the angiotensin II type 1 (AT(1)) receptor. Activation of AT(1) receptors has been linked to pathologic processes that contribute to atherosclerosis and ischemic events, including oxidative stress, inflammatory processes, low-density lipoprotein cholesterol trafficking, and prothrombotic states. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) program will compare the efficacy of the angiotensin II receptor blocker (ARB) telmisartan, the angiotensin-converting enzyme (ACE) inhibitor ramipril, and combination therapy with telmisartan plus ramipril for reducing cardiovascular risk. The ARB telmisartan is distinguished by its long duration of action, which compares favorably with some other ARBs and conventional antihypertensives. Ramipril was shown in the Heart Outcomes Prevention Evaluation (HOPE) study to reduce the risk for myocardial infarction (MI) and other cardiovascular events in patients at high risk for cardiovascular events but without heart failure or a low ejection fraction. The ONTARGET program consists of 2 randomized, double-blind, multicenter international trials: a principal trial, ONTARGET, and a parallel trial, Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease (TRANSCEND). The treatment arms for the principal ONTARGET study are telmisartan 80 mg, ramipril 10 mg, and combination therapy with telmisartan 80 mg plus ramipril 10 mg; for the parallel study TRANSCEND, the treatment arms are telmisartan 80 mg and placebo. Both trials will assess cardiovascular outcomes in patients at high risk using the same criteria as that of the HOPE study, with a single exception: the TRANSCEND trial will enroll patients who do not tolerate ACE inhibitor treatment. The primary end points in both ONTARGET and TRANSCEND are death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. The secondary end points include newly diagnosed heart failure, revascularization, new-onset type 2 diabetes mellitus, nephropathy, cognitive decrease and dementia, and newly diagnosed atrial fibrillation; these will be used for hypothesis generation.

Angiotensin II↗
PubMed2003

Angiotensin II and the fibroproliferative response to acute lung injury.

Angiotensin II (ANG II), generated by activation of local renin-angiotensin systems, is believed to play an important role in tissue repair and remodeling, in part via transforming growth factor-beta (TGF-beta). Angiotensin-converting enzyme (ACE) inhibitors have been shown to abrogate experimental lung injury via a number of potential mechanisms; however, the potentially fibroproliferative role for ANG II in the lung has not been characterized. We hypothesized that, after lung injury, ANG II would stimulate fibroblast procollagen synthesis and promote lung collagen deposition in rats. In vitro, ANG II was a potent inducer of procollagen production in human lung fibroblasts via activation of the type 1 receptor and, at least in part, via the autocrine action of TGF-beta. After bleomycin-induced lung injury, an increase in lung ANG II concentration was observed by day 3 that preceded increases in lung collagen and was maintained until death at day 21. Administration of an ACE inhibitor (ramipril) reduced ACE activity, ANG II concentration, TGF-beta expression, and collagen deposition. Losartan (an ANG II type 1 receptor antagonist) also attenuated the increase in TGF-beta expression and lung collagen deposition. These observations suggest that ANG II, possibly generated locally within the lung, may play an important role in the fibrotic response to acute lung injury, at least in part via the action of TGF-beta. ACE inhibitors and receptor antagonists, already widely used clinically, should be assessed as potential new therapies for fibrotic lung disease.

Acute Disease↗
PubMed2003

Adenosine triphosphate as a stimulant for nociceptive and non-nociceptive muscle group IV receptors in the rat.

For cutaneous and articular nociceptors, adenosine triphosphate (ATP) has been shown to be an effective stimulant. The aim of present study was to find out if among muscle afferents ATP-sensitive group IV receptors are present, and if differences in ATP-responsiveness existed between nociceptive and non-nociceptive units. Single fibre activity was recorded from group IV afferents innervating the rat gastrocnemius-soleus muscle. Using mechanical stimuli the fibres were classified as nociceptive or non-nociceptive ones. ATP was injected intramuscularly into the receptive field of the fibre. Results were: (1) ATP at a concentration that is present in muscle cells elicited excitations in 67% of the fibres; (2) ATP excited both nociceptive and non-nociceptive receptors; and (3) the acidity of the ATP solution was not an important factor for the ATP effect.

Action Potentials↗
PubMed2003

Bradykinin B1 and B2 receptors differentially regulate cardiac Na+-H+ exchanger, Na+-Ca2+ exchanger and Na+-HCO3- symporter.

Bradykinin B(1) and B(2) receptors are up-regulated in the infarcted myocardium, and both receptors are involved in the regulation of intracellular pH and Ca(2+). The present study investigated the role of bradykinin B(1) and B(2) receptors in the regulation of Na(+)-H(+) exchanger (NHE-1), Na(+)-Ca(2+) exchanger (NCE-1) and Na(+)-HCO(3)(-) symporter (NBC-1) in the infarcted myocardium. NHE-1, NCE-1 and NBC-1 mRNA expression was determined by Northern blot analysis and the protein levels by Western blot analysis. Measurements were performed 1, 7 and 14 days after induction of myocardial infarction. Localization of NHE-1, NCE-1 and NBC-1 within the myocardium was studied using confocal microscopy. Cardiac morphology was measured in picrosiris-red-stained hearts. Rats were treated with placebo, the bradykinin B(2) receptor antagonist icatibant (0.5 mg/kg/day) or the bradykinin B(1) receptor antagonist des-Arg(9)-[Leu(8)]bradykinin (1 mg/kg/day). Treatment was started 1 week prior to surgery and continued until 1, 7 and 14 days post infarction. NHE-1, NCE-1 and NBC-1 mRNA expression and protein levels were increased 1 day and reached maximum values on day 7 post infarction. NHE-1 was localized in the plasma membrane, NCE-1 in the membrane of the sarcoplasmatic reticulum and NBC-1 near the Z-line. Icatibant reduced NHE-1 and inhibited NCE-1 mRNA- and protein up-regulation, while des-Arg(9)-[Leu(8)]bradykinin had no effect on NHE-1 and NCE-1 expression and translation. Transcriptional and translational up-regulation of NBC-1 was unaffected by the bradykinin B(1) and B(2) receptor antagonists. Icatibant, but not des-Arg(9)-[Leu(8)]bradykinin, limited infarct size and reduced left ventricular dilation, septal thickening and interstitial fibrosis post infarction. Bradykinin B(2) receptors are involved in transcriptional and translational regulation of NHE-1 and NCE-1 in the ischemic myocardium. Chronic B(2) receptor blockade might exert an anti-ischemic effect via limitation of NHE-1-mediated acidosis and NCE-1-mediated Ca(2+)-overload.

Animals↗
PubMed2003

Differential effect of acute angiotensin II type 1 receptor blockade on the vascular and adrenal response to exogenous angiotensin II in humans.

BACKGROUND: Aldosterone stimulation by angiotensin II may not exclusively be mediated by the angiotensin II type 1 (AT(1)) receptor. We have, therefore, investigated the vascular and adrenal response to angiotensin II infusion without and with pretreatment with the AT(1) receptor antagonist valsartan (160 mg). METHODS: In nine healthy human volunteers, angiotensin II was administered intravenously at doses of 1, 3, and 10 ng/kg/min, each over 45 min. Arterial blood pressure (BP) was measured oscillometrically at 5-min intervals. Blood for the determination of plasma renin activity and aldosterone was taken before the start of the infusion, at the end of each infusion period, and 1 h after the infusion was stopped. RESULTS: Angiotensin II increased systolic and diastolic BP from 121 +/- 3/70 +/- 2 mm Hg to a maximum of 146 +/- 2/97 +/- 1 mm Hg (P <.001) and plasma aldosterone from 39.2 +/- 9.8 to 290.7 +/- 48.3 (P <.001). The increase in BP after exogenous angiotensin II was completely abolished in volunteers pretreated with valsartan, averaging 118 +/- 3/72 +/- 1 mm Hg by the end of the maximum angiotensin infusion dose. In contrast, plasma aldosterone stimulation by angiotensin II was only partially blunted by concomitant AT(1) receptor blockade (98.9 +/- 16.3 pg/mL after the maximal dose of angiotensin II). CONCLUSIONS: These results indicate that although the vascular response to exogenous angiotensin II is exclusively mediated by the AT(1) receptor, the effects of angiotensin II on adrenal aldosterone release may involve other pathways.

Adrenal Glands↗
PubMed2003

Effect of angiotensin AT2 receptor stimulation on vascular cyclic GMP production in normotensive Wistar Kyoto rats.

In the present study in normotensive Wistar Kyoto rats (WKY), we investigated whether any angiotensin II (ANG II) increases in vascular cyclic GMP production were via stimulation of AT(2) receptors. Adult WKY were infused for 4h with ANG II (30 ng/kg per min, i.v.) or vehicle (0.9% NaCl, i.v.) after pretreatment with (1) vehicle, (2) losartan (100 mg/kg p.o.), (3) PD 123319 (30 mg/kg i.v.), (4) losartan+PD 123319, (5) icatibant (500 microg/kg i.v.), (6) L-NAME (1 mg/kg i.v.), (7) minoxidil (3 mg/kg i.v.). Mean arterial blood pressure (MAP) was continuously monitored, and plasma ANG II and aortic cyclic GMP were measured at the end of the study. ANG II infusion over 4h raised MAP by a mean of 13 mmHg. This effect was completely prevented by AT(1) receptor blockade. PD 123319 slightly attenuated the pressor effect induced by ANG II alone (123.4+/-0.8 versus 130.6+/-0.6) but did not alter MAP in rats treated simultaneously with ANG II + losartan (113+/-0.6 versus 114.3+/-0.8). Plasma levels of ANG II were increased 2.2-3.7-fold by ANG II infusion alone or ANG II in combination with the various drugs. The increase in plasma ANG II levels was most pronounced after ANG II+losartan treatment but absent in rats treated with losartan alone. Aortic cyclic GMP levels were not significantly changed by either treatment. Our results demonstrate that the AT(2) receptor did not contribute to the cyclic GMP production in the vascular wall of normotensive WKY.

Angiotensin II↗