Relaxation In Hypertension Research Articles

PENERAPAN METODE RELAKSASI BENSON PADA LANSIA PEREMPUAN DENGAN HIPERTENSI

The elderly is the final stage of the life cycle, and degenerative processes occur in various aspects, which result in a greater risk of exposure to diseases such as hypertension which is usually often found in the elderly. Women are closely related to the occurrence of hypertension when experiencing menopause. Menopausal women experience decreased estrogen, which protects blood vessels from damage. One of the things that can be done to keep blood pressure stable is to use Benson relaxation, which is the development of a relaxation response method involving the belief factor to achieve optimal health conditions. The number of elderly who participated in this training was 17 people. Before the training and presentation of the material, data was obtained that 3 elderly people knew the benefits of Benson relaxation, and 14 people did not know about it. After the training, it was found that 10 elderly people understood Benson relaxation, and 7 other people did not understand this, which means that there was an increase in the understanding of the elderly about the benefits of Benson relaxation in hypertension.
 Keywords: elderly; hypertension; relaxation management

Artemisinin Improves Acetylcholine-Induced Vasodilatation in Rats with Primary Hypertension.

PurposeEndothelial dysfunction and the subsequent decrease in endothelium-dependent vascular relaxation of small arteries are major features of hypertension. Artemisinin, a well-known antimalarial drug, has been shown to exert protecting roles against endothelial cell injury in cardiac and pulmonary vascular diseases. The current study aimed to investigate the effects of artemisinin on endothelium-dependent vascular relaxation and arterial blood pressure, as well as the potential signalling pathways in spontaneously hypertensive rats (SHRs).MethodsIn this study, acetylcholine (ACh)-induced dose-dependent relaxation assays were performed to evaluate vascular endothelial function after treatment with artemisinin. Artemisinin was administered to the rats by intravenous injection or to arteries by incubation for the acute exposure experiments, and it was administered to rats by intraperitoneal injection for 28 days for the chronic experiments.ResultsBoth acute and chronic administration of artemisinin decreased the heart rate and improved ACh-induced endothelium-dependent relaxation but negligibly affected the arterial blood pressure in SHRs. Incubation with artemisinin decreased basal vascular tension, NAD(P)H oxidase activity and reactive oxygen species (ROS) levels, but it also increased endothelial nitric oxide (NO) synthase (eNOS) activity and NO levels in the mesenteric artery, coronary artery, and pulmonary artery of SHRs. Artemisinin chronic administration to SHRs increased the protein expression of eNOS and decreased the protein expression of the NAD(P)H oxidase subunits NOX-2 and NOX-4 in the mesenteric artery.ConclusionThese results indicate that treatment with artemisinin has beneficial effects on reducing the heart rate and basal vascular tension and improving endothelium-dependent vascular relaxation in hypertension, which might occur by increasing eNOS activation and NO release and inhibiting NAD(P)H oxidase derived ROS production.

Abstract MP29: Activation Of Transient Receptor Potential Melastatin 2 (trpm2) Cation Channel Contributes To Nox4-induced Protective Effects In Endothelial Cells.

NOX4-induced H 2 O 2 production promotes vasodilation and is cardiovascular protective. H 2 O 2 also regulates TRPM2, a redox-sensitive channel that regulates Ca 2 influx. eNOS is a Ca 2+ -dependent enzyme, and hypertension-associated endothelial dysfunction involves eNOS inactivation. As NOX4-derived H 2 O 2 regulates TRPM2 and consequently Ca 2+ influx, we questioned whether downregulation of the H 2 O 2 -TRPM2-Ca 2+ axis in endothelial cells may contributes to impaired vascular relaxation in hypertension. WT and TTRhRen hypertensive mice were crossed with Nox4 KO mice. Vascular function was studied in mesenteric resistance arteries by wire myography. Ca 2+ influx was assessed by fluorescence microscopy in aortic endothelial cells, eNOS activation and TRPM2 expression were assessed by immunoblotting and immunohistochemistry, respectively. Blood pressure in TTRhRen (130.3±7.0 mmHg) and TTRhRen/NOX4 KO mice (141.3±18 mmHg) was significantly increased compared to control mice (98.1±8.0 mmHg). Endothelium-dependent relaxation was impaired in TTRhRen mice (Emax: WT 83.5±4.03 vs TTRhRen 59.1±3.5), effects worsened by NOX4 KO (37.9±5.4), p<0.05. Activation of TRPM2 with ADPR, improved vascular relaxation in TTRhRen/NOX4 KO mice (75.9±7.7); an effect also achieved with H 2 O 2 incubation (74.2±15.4), p<0.05. Ang II stimulated H 2 O 2 generation (% of control: 138.23±9.04) followed by Ca 2+ influx (AUC - Ca 2+ : 19401.25±1940.21), an important regulator of eNOS. These processes were reduced by TRPM2 inhibition (AUC - Ca 2+ : 8-br-cADPR 15232.2±1052.0; Olaparib 14260±843.2 and 2-APB 13095.2±277.4, p<0.05) and by the NOX1/4 inhibitor GKT137831 (AUC - Ca 2+ : Ang II 107357±1940.2 vs GKT 15067.5±255.6, p<0.05). Activation of eNOS (Ser1177) by Ang II in endothelial cells was blocked by PEG-catalase, GKT137831, and the TRPM2 inhibitor 8-br-cADPR. TRPM2 inhibitors also increased MAPK expression in endothelial cells. In conclusion, endothelial dysfunction in TTRhRen/NOX4 KO mice involves impaired TRPM2 activation. Reduced bioavailability of H 2 O 2 due to Nox4 downregulation is a major driver of this process. We identify a new axis in endothelial cells involving Nox4-H 2 O 2 -mediated activation of TRPM2-Ca 2+ -eNOS signalling which is vasoprotective.

Aerobic exercise enhanced endothelium-dependent vasorelaxation in mesenteric arteries in spontaneously hypertensive rats: the role of melatonin.

Melatonin, a neuroendocrine hormone synthesized primarily by the pineal gland, provides various cardiovascular benefits. Regular physical activity is an effective non-pharmacological therapy for the prevention and control of hypertension. In the present study, we hypothesized that melatonin plays an important role in the aerobic exercise-induced increase of endothelium-dependent vasorelaxation in the mesenteric arteries (MAs) of spontaneously hypertensive rats (SHRs) in a melatonergic receptor-dependent manner. To test this hypothesis, we evaluated the vascular mechanical and functional properties in normotensive Wistar Kyoto (WKY), SHRs, and SHRs that were trained on a treadmill (SHR-EX) for 8 weeks. Exercise training produced a significant reduction in blood pressure and heart rate in SHR, which was significantly attenuated by the intraperitoneal administration of luzindole, a non-selective melatonin receptor (MT1/MT2) antagonist. Serum melatonin levels in the SHR group were significantly lower than those in the WKY group at 8:00-9:00 and 21:00-22:00, while exercise training reduced this difference. Endothelium-dependent vessel relaxation induced by acetylcholine was significantly blunted in SHR compared with age-matched WKY. Both exercise training and luzindole ameliorated this endothelium-dependent impairment of relaxation in hypertension. Immunohistochemistry and Western blotting showed that the protein expression of the MT2 receptor and eNOS, as well as their colocalization in the endothelial cell layer in SHRs, was significantly decreased; as exercise training suppressed this reduction. These results provide evidence that regular exercise has a beneficial effect on improving endothelium-dependent vasorelaxation in MAs, in which melatonin plays a critical role by acting on MT2 receptors to increase NO production and/or NO bioavailability.

The Role of Melatonin In Exercise Enhanced Endothelium-dependent Vasorelaxation In Mesenteric Arteries of SHR

PURPOSE: To determine if melatonin plays an important role in the hypotensive effects of exercise training. Further, to study the role of melatonin binding to melatonergic receptors in the vasorelaxation of small MAs in SHR. METHODS: Twelve-week-old male normotensive Wistar-Kyoto rats (WKY, n=18) and SHRs (n = 48) were used. SHRs were randomly divided into four groups: SHR sedentary group (SHR-SED, n = 18), SHR sedentary with melatonin receptor antagonist luzindole (Luz) injection group (SHR-SED + Luz, n = 6), SHR exercise group (SHR- EX, n = 18) , and SHR exercise with luzindole injection group (SHR-EX + Luz, n = 6). Luzindole injection groups were injected intraperitoneally (i.p.) with luzindole (1 mg/ kg/day in sterile saline) each day. Rats in the exercise groups were subjected to aerobic exercise. Blood pressure and heart rate were measured after exercise. Serum melatonin levels were examined by ELISA. The mechanical properties of small mesenteric arteries were studied with myograph. Western blot and immunofluorescence colocalization were performed to examine the protein expression and distribution of MT1, MT2 receptors and eNOS. RESULTS: Exercise training produced a significant reduction in blood pressure and heart rate in SHR, which was significantly attenuated by intraperitoneal administration of luzindole, a nonselective melatonin receptor (MT1/MT2) antagonist. Serum melatonin levels in the SHR group were significantly lower than those in the WKY group at 8:00-9:00 and 21:00-22:00, and exercise training reduced this difference. Endothelium-dependent vessel relaxation induced by acetylcholine was significantly blunted in SHR compared with age-matched WKY. Both exercise training and luzindole ameliorated this endothelium-dependent impairment of relaxation in hypertension. Immunohistochemistry and Western blotting showed that protein expression of the MT2 receptor and eNOS, as well as their colocalization in the endothelial cell layer in SHR, was significantly decreased; exercise training suppressed this reduction. CONCLUSIONS: These results provide evidence that regular exercise has a beneficial effect on improving endothelium-dependent vasorelaxation in MAs, in which melatonin plays a critical role by acting on MT2 receptor to increase NO production and/or NO bioavailability.

Crocetin, a Carotenoid Derived from Saffron (Crocus sativus L.), Improves Acetylcholine-Induced Vascular Relaxation in Hypertension

Background: Hypertension is associated with endothelial dysfunction characterized by decreased vasorelaxation. Crocetin, a bioactive compound of saffron, exhibits favorable cardiovascular properties. We analyze the vasomodulatory effects of crocetin in hypertension. Methods: Myographical experiments were performed to compare the relaxation induced by acetylcholine (ACH) on aortic rings from normotensive (Wistar) and hypertensive (SHR) rats, incubated with or without crocetin or saffron extract and <smlcap>L</smlcap>-NAME or indomethacin. Extracts were also assayed in deendothelialized rings. UV-vis spectrophotometry and HPLC-DAD were used to characterize and quantify the saffron used. Results: Crocetin enhanced the ACH relaxations in aorta from hypertensive (strongly) and normotensive rats (weakly). Saffron extract did not modify this. Crocetin plus <smlcap>L</smlcap>-NAME abolished the relaxant response in SHR but not in Wistar aorta. Crocetin plus indomethacin did not modify the indomethacin response in either SHR or Wistar aorta. Crocetin in rubbed segments did not modify the ACH responses. In contrast, saffron increased this response in rubbed segments from SHR but not Wistar rats. Conclusion: Crocetin exerts healthy vasomodulatory effects in hypertension, strongly improving endothelium-dependent ACH relaxations via endothelial nitric oxide but not the cyclooxygenase pathway. This work proposes that crocetin supplements are a possible complement in the therapy of hypertension.

Immediate Effect of Jacobson's Progressive Muscular Relaxation in Hypertension

Objective: To study the effectiveness of Jacobson's relaxation techniques as an adjunct therapy in control of hypertension. Design: A Experimental study. Setting: Constituent colleges of Pravara Institute of Medical Sciences (Deemed University) and the colleges of Pravara Rural Education Society in the vicinity. Cardio-respiratory Physiotherapy Department, College of Physiotherapy & Pravara Rural Hospital (Tertiary Hospital), Loni, Tal- Rahata, Dist- Ahmednagar , Maharashtra State, India- 413 736. Participants: A total of 250 college teachers were screened for hypertension. Out of which 105 subjects were found suitable and willing for participation in the study. Interventions: Jacobson's progressive muscle relaxation lying in supine position for 30 minutes. Main outcome measures: Blood pressure and Heart rate. Results: Significant difference was noted in systolic & diastolic blood pressure and heart rate immediately after 30 minutes of Jacobson's progressive muscular relaxation technique. Conclusions: Jacobson's progressive muscular relaxation may be used as an adjuvant therapy for immediate control of hypertension. Clinical Trial Registration Number: (PMT/PIMS/RC/ 2012/06)

Real-Time Three-Dimensional Echocardiography in the Evaluation of Left Atrial Structure and Function in Normal, Aging, Hypertensive and Heart Failure Patients: New Insights into Left Atrial Adaptation and Remodeling

Precise left atrial (LA) volume quantification, representative of LA function, is of extraordinary clinical prognostic value. However, a detailed description of pathophysiology in different disease populations and interactions with aging by real-time three-dimensional echocardiography (RT-3DE) is lacking. This study consisted of three protocols: (1) to test the impact of different LA cutting planes on LA volume quantification in different disease populations ( n = 61) by RT-3DE; (2) to examine the impact of aging, hypertension ( n = 145), the interaction on LA remodeling; and (3) to further depict the LA regional and global remodeling process in different disease entities ( n = 68), including heart failure (HF). Bias and percentage error in LA volume quantification tended to decrease significantly when compared with the automatic border detection method at eight cutting planes. A linear relationship was apparent between maximal LA volume and age in the hypertensive group ( r = 0.26, p = 0.03), but not in the normal aging group ( r = 0.16, p = 0.19). A significantly reduced pumping fraction and enlarged LA volume was observed in HF patients ( p < 0.01), with a trend toward less LA pumping volume ( p = 0.1). Eight cut planes provided sufficient accuracy in LA volume quantification using the RT-3DE method. Compared with normal aging, LA volume tends to increase with higher pumping volume to compensate for impaired left ventricular relaxation in hypertension. Relatively preserved total LA pumping volume may exist in heart failure patients at the expense of further adaptive volume expansion with a subsequently reduced total emptying fraction.

Enhanced G-protein coupled receptors-mediated contraction and reduced endothelium-dependent relaxation in hypertension

The present study was designed to demonstrate a hypothesis that some G-protein coupled receptors are up-regulated and a dysfunction of endothelium occurs in hypertension. The arteries from hypertensive patients and spontaneously hypertensive rats (SHR) were tested. An in vitro myograph system was used to obtain concentration–contraction curves mediated by endothelin ET A, endothelin ET B, 5-hydroxytryptamine 2A (5-HT 2A)-receptors and α 1-adrenoceptors in the arterial segments. In hypertensive patients, the maximum contractions ( E max) induced by endothelin ET B, endothelin ET A and 5-HT receptors were significantly increased with elevated pEC 50 values, while a significantly leftward shift of α 1-adrenoceptor-mediated contraction was seen. Similar results were obtained in SHR. Specific antagonists for 5-HT 2A receptors or α 1-adrenoceptors rightward shifted the concentration–contractile curves induced by 5-HT or noradrenalin, while the E max were not significantly altered, suggesting that the contractions were mediated by 5-HT 2A receptors and α 1-adrenoceptors, respectively. Endothelium-dependent maximum relaxation ( R max) in the arterial segments induced by acetylcholine was significantly decreased in both hypertensive patients and SHR. In addition, nitric oxide- and endothelium-derived hyperpolarizing factor-mediated dilatations were decreased significantly and the arterial endothelial cells were in part lost in SHR. In conclusion, endothelin ET B, endothelin ET A, 5-HT 2A receptor- and alpha-adrenoceptor-mediated contractions were increased in hypertension, while the endothelium and its functions were damaged.

Left ventricular concentric geometry is associated with impaired relaxation in hypertension: the HyperGEN study

We tested the hypothesis that abnormal left ventricular (LV) relaxation is associated with concentric LV geometry. Doppler LV filling properties were studied in 1384 hypertensive participants without cardiovascular disease, from the HyperGEN population (731 women, 784 obese, 236 diabetic) and compared in four LV geometry groups; normal, concentric remodelling (3.5%), eccentric (23%), and concentric LV hypertrophy (4%), based on echocardiographic LV mass index (in g/m(2.7)). Abnormal LV relaxation was identified by European Society of Cardiology criteria in 275 subjects (20%). After accounting for significant confounders, E/A ratio and isovolumic relaxation time were not related to the presence of LV hypertrophy, but indicated abnormal relaxation when LV geometry was concentric (both P<0.0001). Deceleration time of E velocity was prolonged with LV hypertrophy (P<0.03), but the behaviour in relation to concentric LV geometry differed in the presence (prolonged) or absence (reduced) of LV hypertrophy (P=0.05), a difference independently related to the magnitude of both transmitral gradients and stroke volume (all P<0.05). Logistic regression showed that, compared with normal LV geometry, the odds of abnormal LV relaxation was 2.3-fold greater when LV geometry was concentric and that LV hypertrophy conferred a borderline higher risk than normal LV mass. In hypertensive individuals without prevalent cardiovascular disease from a multi-ethnic population-based sample, delayed LV relaxation is independently associated with concentric LV geometry.

1142-186 Elevated levels of circulating tissue inhibitor of metalloproteinase-1 correlate with impaired diastolic relaxation in hypertension: Implications for diastolic heart failure

1142-186 Elevated levels of circulating tissue inhibitor of metalloproteinase-1 correlate with impaired diastolic relaxation in hypertension: Implications for diastolic heart failure

The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls superoxide release from endothelial nitric oxide synthase: an EPR spin trapping study.

Augmentation of superoxide levels has been linked to impaired relaxation in hypertension, diabetes and hypercholesterolaemia. Purified endothelial nitric oxide synthase (eNOS) generates superoxide under limited availability of 5,6,7,8-tetrahydrobiopterin (BH(4)). Thus alterations in endothelial BH(4) levels have been postulated to stimulate superoxide production from eNOS. This possibility was examined by determining the concentration-dependent effects of BH(4), and its analogues, on superoxide formation by eNOS. Superoxide was quantified by EPR spin trapping, which is the only available technique to quantify superoxide from eNOS. Using 5-ethoxycarbonyl-5-methyl-pyrroline N-oxide, we show that only fully reduced BH(4) diminished superoxide release from eNOS, with efficiency BH(4)>6-methyl-BH(4)>5-methyl-BH(4). In contrast, partially oxidized BH(4) analogues, 7,8-dihydrobiopterin (7,8-BH(2)) and sepiapterin had no effect. Neither l-arginine nor N(G)-nitro-l-arginine methyl ester (l-NAME) abolished superoxide formation. Together, BH(4) and l-arginine stimulated .NO production at maximal rates of 148 nmol/min per mg of protein. These results indicate that BH(4) acts as a "redox switch", decreasing superoxide release and enhancing .NO formation. This role was verified by adding 7,8-BH(2) or sepiapterin to fully active eNOS. Both 7,8-BH(2) and sepiapterin enhanced superoxide release while inhibiting (.)NO formation. Collectively, these results indicate that the ratio between oxidized and reduced BH(4) metabolites tightly regulates superoxide formation from eNOS. The pathological significance of this scenario is discussed.

The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls superoxide release from endothelial nitric oxide synthase: an EPR spin trapping study

Augmentation of superoxide levels has been linked to impaired relaxation in hypertension, diabetes and hypercholesterolaemia. Purified endothelial nitric oxide synthase (eNOS) generates superoxide under limited availability of 5,6,7,8-tetrahydrobiopterin (BH4). Thus alterations in endothelial BH4 levels have been postulated to stimulate superoxide production from eNOS. This possibility was examined by determining the concentration-dependent effects of BH4, and its analogues, on superoxide formation by eNOS. Superoxide was quantified by EPR spin trapping, which is the only available technique to quantify superoxide from eNOS. Using 5-ethoxycarbonyl-5-methyl-pyrroline N-oxide, we show that only fully reduced BH4 diminished superoxide release from eNOS, with efficiency BH4&amp;gt;6-methyl-BH4&amp;gt;5-methyl-BH4. In contrast, partially oxidized BH4 analogues, 7,8-dihydrobiopterin (7,8-BH2) and sepiapterin had no effect. Neither l-arginine nor NG-nitro-l-arginine methyl ester (l-NAME) abolished superoxide formation. Together, BH4 and l-arginine stimulated ˙NO production at maximal rates of 148nmol/min per mg of protein. These results indicate that BH4 acts as a ‘redox switch’, decreasing superoxide release and enhancing ˙NO formation. This role was verified by adding 7,8-BH2 or sepiapterin to fully active eNOS. Both 7,8-BH2 and sepiapterin enhanced superoxide release while inhibiting ˙NO formation. Collectively, these results indicate that the ratio between oxidized and reduced BH4 metabolites tightly regulates superoxide formation from eNOS. The pathological significance of this scenario is discussed.

A critical review of the role of endothelial factors in the pathogenesis of hypertension.

The endothelium produces a variety of substances that play important roles in regulation of the circulation and vascular wall homeostasis. The control of blood vessel wall homeostasis is achieved via production of vasorelaxants and vasoconstrictors. Among the vasorelaxants are nitric oxide (NO), prostacyclin, various endothelium-derived hyperpolarizing factors (EDHFs, such as cytochrome P-450 monooxygenase metabolites of arachidonic acid like epoxyeicosatrienoic acids, and endocannabinoids), and C-type natriuretic peptide. Among the vasoconstrictors we find endothelin-1 (ET-1) and endothelium-derived contracting factors (EDCF) that are cyclooxygenase products such as endoperoxides and thromboxanes. The endothelium, via these and other agents, also exerts a critical influence on the blood stream, particularly formed elements such as leucocytes and platelets, and on substances involved in blood coagulation. All these effects contribute to modulating the growth of the vascular wall in hypertension, and participate in the development of atherothrombotic complications associated with hypertension. Inhibition of NO production may induce elevation of blood pressure in experimental animals. However, even today, we do not have incontrovertible evidence of participation of NO, EDHFs or EDCFs, or other endothelial products, in the pathogenesis of hypertension, although there is evidence of abnormal endothelium-dependent relaxation in hypertension in many but not all hypertensives. It is unclear, however, to what extent this may precede hypertension or be a consequence of elevated blood pressure, possibly contributing to its complications. Also, it is often difficult to dissociate abnormal endothelium-dependent relaxation from confounding factors such as the presence of associated conditions like dyslipidaemia, diabetes, smoking, obesity, hyperhomocysteinaemia, and others, that are accompanied themselves by abnormal endothelium-dependent relaxation. There is some evidence for a role of ET-1 in blood pressure elevation in some experimental forms of hypertension, particularly severe, sodium-sensitive hypertension, in which it may play a role in accentuating rather than initiating blood pressure elevation. Endothelin-1 may play a similar role in human hypertension.

Pulsed tissue doppler images of myocardial relaxation in hypertension: relation to pulsed transmitral flow velocity ratio

Pulsed tissue doppler images of myocardial relaxation in hypertension: relation to pulsed transmitral flow velocity ratio

Endothelium-dependent relaxation and hyperpolarization in aorta from control and renal hypertensive rats.

Endothelium-dependent relaxations are depressed in hypertension. In this study we investigated the possible involvement of endothelium-dependent smooth muscle hyperpolarization in this phenomenon. In isolated aortic segments from control rats, acetylcholine (10(-8)-10(-5) M) elicits relaxations after precontraction with norepinephrine (10(-7) M), and acetylcholine or carbachol (10(-5) M) induce smooth muscle hyperpolarization (10.6 +/- 0.9 mV). Both effects disappear after removal of the endothelium and are depressed by tetraethylammonium (3 x 10(-3) M), a rather nonspecific blocker of K+ channels, but not by glibenclamide (10(-5) M), a potent blocker of the ATP-regulated K+ channels, which has a marked effect on the relaxation induced by BRL 38227. The relaxation effect of acetylcholine is impaired in norepinephrine-contracted preparations from hypertensive rats but is not further depressed by tetraethylammonium. In aorta from hypertensive rats, hyperpolarization induced by carbachol was significantly reduced to a mean of only 21.8% of the values obtained in preparations from normotensive rats. From the relaxation-hyperpolarization relation obtained with BRL 38227 (opening K+ channels), it is derived that the endothelium-dependent hyperpolarization (approximately 10 mV) contributes for at least 20-30% of the maximal relaxation effect of acetylcholine on rat aorta. It is concluded that the diminished endothelium-dependent hyperpolarization may contribute to the depression of the endothelium-dependent relaxation in hypertension.

Relaxation in hypertension.

Hypotensive drug therapy may be withdrawn or reduced if relaxation techniques are used to control mild hypertension.

Depressed endothelium-dependent relaxation in hypertension: relation to increased blood pressure and reversibility.

Endothelium-dependent relaxation effects have been reported to be impaired in thoracic aorta from genetic and experimentally induced hypertensive rats. This study extends these observations to carotid artery and abdominal aorta from renovascular hypertensive rats. It was also found that rats with coarctation of aorta show depressed endothelium-dependent relaxation responses in thoracic aorta above the stenosis (high pressure region) while no depressed responses are observed in abdominal aorta below the stenosis (normal pressure region). Reversibility of the depression of endothelium-dependent relaxation was investigated on aorta from renovascular hypertensive rats in which blood pressure was normalized by removal of the stenotic kidney three months after induction of hypertension. Endothelium-dependent responses were restored partially after 1-2 weeks and completely after two months of normalization of blood pressure. These results indicate that the increased blood pressure is indeed the causative factor responsible for the impaired endothelium-dependent relaxations in arteries from experimental hypertensive rats, a phenomenon which is reversible, at least in our experimental conditions.

The loss of endothelium-dependent vascular relaxation in hypertension.

We investigated endothelium-dependent relaxation in rat aortae, using three models of experimental hypertension: deoxycorticosterone and salt; one-kidney, one clip renovascular hypertension; and coarctation. Isolated aortae were contracted with phenylephrine, and relaxation was subsequently induced with acetylcholine or calcium ionophore A23187. Blood vessels denuded of endothelium did not relax in response to acetylcholine or A23187. Blood vessels from animals with high blood pressure had decreased relaxation responses to acetylcholine and A23187, and also to the endothelium-independent vasodilator sodium nitroprusside. Unlike acetylcholine and A23187, however, nitroprusside completely relaxed the blood vessels from the hypertensive animals, though the sensitivity to nitroprusside was much lower in these vessels. Subsequent reversal of hypertension caused a return of endothelium-dependent relaxation. Loss of endothelium-dependent relaxation occurs readily in the aortae with the development of hypertension; this phenomenon appears to be related to elevated pressure.

Blood pressure and heart-rate response to verbal instruction and relaxation in hypertension.

Recent data have suggested that instructional set and task awareness may play a substantial role in the achievement of directional changes in blood pressure associated with “operant conditioning” techniques. Six hypertensive patients were instructed alternately to raise (UP) and lower (DOWN) their blood pressure by concentrating on changing “heart rate, force of contraction, and blood vessel resistance to flow.” Paired 10 min periods were separated by the experimenter's entry and exit. Five of the subjects were taught progressive muscular relaxation (PMR), and the protocol repeated, with PMR induced throughout this session. The immediate cardiovascular response to PMR, induced in both the presence and absence of the experimenter, was studied. Systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) were measured every 30 sec in all sessions. Direction of changes in BP and HR for UP and DOWN periods was appropriate and significant in both instruction sessions, and these differences for BP frequently reached significant levels of magnitude. In general, interactions for HR did not reach significant levels. Comparison of the two sessions yielded little difference between them. PMR uniformly lowered BP and HR, but was of significant magnitude only when induction of PMR involved the active participation of the experimenter. Interview data revealed considerable dramatic mental imagery associated with directional shifts in BP. The results indicate that directional instruction may result in appropriate changes in BP and HR of a magnitude comparable to those reported in studies using “external biofeedback.” PMR did not alter the response. This study adds to other data which point to the potential for nonspecific or “placebo” effects to be operative in conditioning studies.