Vascular Reactivity in Post-Deoxycorticosterone Hypertension in Rats and its Relation to ‘Irreversible’ Hypertension in Man

1972 ◽  
Vol 42 (5) ◽  
pp. 579-590 ◽  
Author(s):  
L. J. Beilin ◽  
G. Ziakas
Keyword(s):  
Blood Pressure ◽  
High Pressure ◽  
Vascular Reactivity ◽  
Renal Hypertension ◽  
Peripheral Resistance ◽  
Systemic Resistance ◽  
Wall Thickening ◽  
Resistance Vessels ◽  
Arteriolar Wall ◽  
Rat Tail

1. The mechanism by which the blood pressure remains elevated after temporary administration of deoxycorticosterone (DOCA) and saline has been studied by comparing vascular reactivity in the resistance bed of the isolated perfused rat tail in animals with post-DOCA hypertension and normotensive controls. 2. Animals with post-DOCA hypertension showed increased arteriolar responses to noradrenaline and 5-hydroxytryptamine, increased maximum contractile responses to noradrenaline, and increased resistance to flow under conditions of maximum vasodilation. 3. These abnormalities may be explained largely on the basis of arteriolar wall thickening resulting from hypertension and they will lead to a high peripheral resistance. 4. Evidence from experiments on chronic renal hypertension indicates that hypertension only becomes irreversible when the ability of the kidneys to regulate blood pressure is impaired. When this has occurred the high resistance offered by abnormal systemic arterioles will be a significant factor in maintaining a high arterial pressure and the high pressure will in turn continue to exert deleterious effects on resistance vessels, including those of the kidney. 5. It is suggested that persistence of hypertension in patients in whom the initial cause of the hypertension has apparently been removed is due to changes in morphology and reactivity of renal and systemic resistance vessels similar to those described in arterioles of animals with post-DOCA hypertension.

Total autonomic blockade eliminates the attenuated pressor response to angiotensin II in pregnant rats

1993 ◽  
Vol 265 (6) ◽  
pp. R1270-R1275
Author(s):  
T. Hines ◽  
M. D. Lindheimer ◽  
W. M. Barron
Keyword(s):  
Angiotensin Ii ◽  
Repeated Measures ◽  
Vascular Reactivity ◽  
Peripheral Resistance ◽  
Systemic Resistance ◽  
Bolus Administration ◽  
Ang Ii ◽  
Pregnant Rats ◽  
Pressor Responses ◽  
Autonomic Blockade

Pressor responses to angiotensin II (ANG II) are markedly attenuated in reflex-intact pregnant animals, a phenomenon widely attributed to intrinsic changes in vascular reactivity. To test the hypothesis that gestational augmentation of neural reflex activity contributes importantly to this phenomenon, changes in mean arterial pressure (MAP), cardiac output (CO), and total peripheral resistance (TPR) were compared during constant infusion (25-400 ng.kg-1.min-1) of ANG II in conscious virgin and pregnant rats, using a model of total autonomic blockade (chlorisondamine chloride and methscopolamine bromide), with restoration of baseline hemodynamics by infusion of norepinephrine. Basal CO was higher and TPR lower in pregnant (CO 121.8 +/- 3.8 ml/min; TPR 0.78 +/- 0.04 mmHg.ml-1.min) compared with virgin (CO 95.9 +/- 3.9 ml/min; TPR 1.05 +/- 0.08 mmHg.ml-1.min) rats (P < 0.005). Pressor responses to ANG II were similar in both groups of reflex-blocked animals due to comparable changes in TPR and CO (not significant by repeated-measures analysis of variance). Other experiments demonstrated that changes in MAP after bolus administration of ANG II did not differ in areflexic virgin and gravid rats. Thus in the absence of autonomic control ANG II has similar effects on systemic resistance in pregnant and nonpregnant rats, suggesting that reflex neural mechanisms contribute significantly to gestational changes in pressor responsiveness. These data further suggest that pregnancy is not accompanied by a generalized decrease in vascular reactivity to all pressor agents.

Cardiopulmonary reflexes and blood pressure in exercising sinoaortic-denervated dogs

1984 ◽  
Vol 57 (5) ◽  
pp. 1417-1421 ◽  
Author(s):  
D. A. Daskalopoulos ◽  
J. T. Shepherd ◽  
S. C. Walgenbach
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Vagal Afferents ◽  
Systemic Resistance ◽  
Vigorous Exercise ◽  
Arterial Blood ◽  
Resistance Vessels ◽  
Before And After ◽  
Cervical Vagotomy ◽  
Cardiopulmonary Receptors

To examine the role of cardiopulmonary receptors in arterial blood pressure regulation during and after exercise, conscious dogs with chronic sinoaortic denervation were subjected to 12 min of light exercise and 12 min of exercise that increased in severity every 3 min. Hemodynamic measurements were made before and after interruption of cardiopulmonary afferents by bilateral cervical vagotomy. During both exercise protocols, after an initial transient decrease, the arterial blood pressure remained close to resting values before and after vagotomy. On cessation of the graded exercise, the arterial blood pressure did not change before, but a rapid and sustained increase in pressure occurred after vagotomy. At the time of this increase the cardiac output and heart rate were returning rapidly to the resting level. The study demonstrates that in the chronic absence of arterial baroreflexes, vagal afferents prevent a rise in arterial blood pressure after vigorous exercise presumably by the action of cardiopulmonary receptors causing a rapid dilatation of systemic resistance vessels.

Mechanism of Early and Chronic Experimental Renal Hypertension as Tested by CCK-179

1956 ◽  
Vol 186 (1) ◽  
pp. 161-166 ◽  
Author(s):  
Irene H. Oyen
Keyword(s):  
Blood Pressure ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Renal Hypertension ◽  
Peripheral Resistance ◽  
Repeated Administration ◽  
Maximal Effect ◽  
Renal Effects ◽  
Experimental Renal Hypertension

The effects on blood pressure and renal clearances of a combination of dihydrogenated ergot alkaloids, CCK-179, were studied in normal dogs and dogs with experimental renal (Goldblatt) hypertension. The drug was observed to have a maximal effect at 0.012 mg/kg, about one twelfth to one sixteenth the dose recommended in the literature. In normal dogs the drug causes a slight fall in blood pressure, a moderate decrease in glomerular filtration rate (creatinine clearance) and a pronounced decrease in renal plasma flow (PAH clearance), hemodynamic effects resembling those seen in man. After repeated administration of the drug, the renal effects are of greater magnitude in these dogs. In hypertensive dogs, CCK-179 causes blood pressure to approach normal levels. In the early weeks of hypertension, the renal effects of the drug are similar to those seen in normals but as hypertension increases in duration up to 55 weeks, the decreases in filtration rate and plasma flow become progressively smaller. This could indicate that in chronic experimental renal hypertension the high peripheral resistance is maintained at least in part by increased activity of the sympathetic nervous system rather than by the action of the components of the renal humoral pressor system.

Critical opening pressure and reactivity of tail vessels in conscious hypertensive rats

1976 ◽  
Vol 54 (3) ◽  
pp. 314-321
Author(s):  
A. C. Darke ◽  
P. G. Nair ◽  
P. Gaskell
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Vascular Reactivity ◽  
Experimental Hypertension ◽  
Hypertensive Rats ◽  
Opening Pressure ◽  
Critical Opening ◽  
Resistance Vessels ◽  
Before And After ◽  
Desoxycorticosterone Acetate

The possible role of increased vascular reactivity in the mechanism of experimental hypertension was studied by measurements of the critical opening pressure (COP) of tail vessels in conscious rats. In hypertension induced by administration of desoxycorticosterone acetate (DOCA) and replacement of the drinking water by 1% NaCl solution (DOCA–NaCl hypertension), and in one-kidney Goldblatt renovascular hypertension, the raised level of blood pressure was associated with an increased COP of the tail vessels when measured both before and after ganglionic blockade. In rats treated with either DOCA alone or 1% NaCl alone there was no significant increase in systolic blood pressure (SBP) or COP relative to the corresponding controls. In all four experimental series intravenous infusion of angiotensin or norepinephrine in conscious ganglion-blocked rats produced dose-dependent increases in SBP and COP. In DOCA–NaCl hypertensive rats but not in renovascular hypertensives, nor in rats treated with DOCA alone or 1% NaCl alone, the increase in COP for a given increment in dose of angiotensin or norepinephrine was significantly greater than in the control rats. It is concluded that in DOCA–NaCl hypertension there is a true increase in the reactivity of the smooth muscle of the resistance vessels to angiotensin and norepinephrine. In renovascular hypertension this is not the case and other factors must therefore be involved in causing the increased blood pressure and COP.

Potent cardiovascular actions of homologous adrenomedullins in eels

2008 ◽  
Vol 294 (5) ◽  
pp. R1544-R1553 ◽  
Author(s):  
Shigenori Nobata ◽  
Maho Ogoshi ◽  
Yoshio Takei
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Peripheral Resistance ◽  
Cardiovascular Effects ◽  
Dorsal Aorta ◽  
Minimum Effective Dose ◽  
Cardiovascular Actions ◽  
Resistance Vessels ◽  
Ventral Aorta ◽  
Specific Receptors

Adrenomedullin (AM), known as a multifunctional hormone in mammals, forms a unique family of five paralogous peptides in teleost fish. To examine their cardiovascular effects using homologous AMs in eels, we isolated cDNAs encoding four eel AMs, and named AM1 (ortholog of mammalian AM), AM2, AM3 (paralog of AM2 generated only in teleost lineage), and AM5 according to the known teleost AM sequences. Unlike pufferfish, not only AM1 but AM2/3 and AM5 were expressed ubiquitously in various eel tissues. Synthetic mature AM1, AM2, and AM5 exhibited vasodepressor effects after intra-arterial injections, and the effects were more potent at dorsal aorta than at ventral aorta. This indicates that AMs preferentially act on peripheral resistance vessels rather than on branchial arterioles. The potency was in the order of AM2 = AM5 ≫ AM1 in both freshwater (FW) and seawater (SW) eels, which is different from the result of mammals in which AM1 is as potent as, or more potent than, AM2 when injected peripherally. The minimum effective dose of AM2 and AM5 in eels was 1/10 that of AM1 in mammals. The hypotension reached 50% at 1.0 nmol/kg of AM2 and AM5, which is much greater than atrial natriuretic peptide (20%), another potent vasodepressor hormone. Even with such hypotension, AMs did not change heart rate in eels. In addition, AM1 increased blood pressure at ventral aorta and dorsal aorta immediately after an initial hypotension at 5.0 nmol/kg, but not with AM2 and AM5. These data strongly suggest that specific receptors for AM2 and AM5 exist in eels, which differ from the AM1 receptors identified in mammals.

Selected Contribution: Altered vascular reactivity in arterioles of chronic intermittent hypoxic rats

2001 ◽  
Vol 90 (5) ◽  
pp. 2007-2013 ◽  
Author(s):  
Ziad Tahawi ◽  
Natalia Orolinova ◽  
Irving G. Joshua ◽  
Michael Bader ◽  
Eugene C. Fletcher
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Vascular Reactivity ◽  
Peripheral Resistance ◽  
Separate Experiment ◽  
Systemic Hypertension ◽  
Endothelin 1 ◽  
Arterial Blood ◽  
And Control ◽  
Baseline Diameter

Recurrent episodic hypoxia (EH) is a feature of sleep apnea that may be responsible for some chronic cardiovascular sequelae such as systemic hypertension. Chronic EH (8 h/day for 35 days) causes elevation of diurnal resting (unstimulated) mean arterial blood pressure (MAP) in the rat. We used in vivo video microscopy to examine arteriolar reactivity in the cremaster muscle of male Sprague-Dawley rats subjected to 35 days of EH. Cremaster muscles of EH ( n= 6) and control ( n = 6) rats were exposed to varying doses of norepinephrine (NE) (10−10 to 10−5M), ACh (10−9 to 10−5 M), and endothelin-1 (10−12 to 10−8 M). In a separate experiment, EH ( n = 5) and control ( n = 6) rats were given one dose of a nitric oxide synthase (NOS) inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 10−5 M). We also examined endothelial NOS mRNA from the kidneys of EH-stimulated and control (unstimulated) rats. Telemetry-monitored EH rats showed a 16-mmHg increase in MAP over 35 days, whereas control rats showed no change. The response to NE and endothelin-1 were similar for EH and control rats. ACh vasodilatation of arterioles in EH rats was significantly attenuated compared with that of controls. The degree of vasoconstriction in response to blockade of the nitric oxide system byl-NAME was significantly less (83% of baseline diameter with l-NAME) for arterioles of EH rats compared with that for controls (61% of baseline diameter), implying lower basal resting nitric oxide release in the EH rats. Whole kidney mRNA endothelial NOS levels were not different between groups. These data support the hypothesis that chronic elevation of blood pressure associated with EH involves increased peripheral resistance from decreased basal release or production of nitric oxide after 35 days of EH.

Evidence for a Decreased Noradrenaline Sensitivity in Mesenteric Resistance Vessels from Rats with Chemical Renal Medullectomy

1989 ◽  
Vol 77 (2) ◽  
pp. 167-170 ◽  
Author(s):  
S. J. Bund ◽  
A. M. Heagerty ◽  
A. Fletcher ◽  
J. D. Swales
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Intraperitoneal Injection ◽  
Wistar Rats ◽  
Vascular Reactivity ◽  
Morphological Changes ◽  
Pressor Responses ◽  
Resistance Vessels

1. Chemical renal medullectomy was performed in Wistar rats by intraperitoneal injection of 2-bromoethylamine hydrobromide (200 mg/kg body weight). The effect of this treatment upon blood pressure and mesenteric vascular reactivity and morphology was studied 3 weeks after treatment. 2. Blood pressure was significantly raised in medull-ectomized rats. The indirect systolic pressures (means ± sem) were 112 ± 2.4 mmHg (14.9 ± 0.32 kPa) and 123 ± 3.5 mmHg (16.4 ± 0.5 kPa) (P < 0.02) for control (n = 12) and medullectomized (n = 12) rats, respectively. However, there were no significant changes in the morphology of the mesenteric resistance vessels. 3. Maximum pressor responses and Ca2+ sensitivities were unchanged in these vessels compared with controls, but the sensitivity to noradrenaline was significantly reduced. Noradrenaline pD2 (= −log ED50) values (means ± sem) were 5.87 ± 0.03 and 5.69 ± 0.08 (P < 0.05) for control (n = 12) and medullectomized (n = 12) rats, respectively. 4. This study demonstrates that in this model of hypertension the noradrenaline sensitivity is reduced in mesenteric resistance vessels, but there are no detectable morphological changes associated with the rise in blood pressure.

Cardiovascular medicine

2019 ◽  
Author(s):  
Stevan R. Emmett ◽  
Nicola Hill ◽  
Federico Dajas-Bailador
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Output ◽  
Nucleus Tractus Solitarius ◽  
Disease Risk ◽  
Peripheral Resistance ◽  
Feedback Mechanism ◽  
Systemic Resistance ◽  
Cardio Vascular Disease ◽  
Cardio Vascular

Hypertension (HTN) is the most common condition man¬aged in primary care and a major risk factor for cardio-vascular disease. Numerous randomized controlled trials have demonstrated that the use of antihypertensives to manage blood pressure (BP) helps reduce cardiovascular disease risk. Prevalence of HTN increases with age so that around 33% of men and 25% of women aged 45– 54 years have a clinical diagnosis. It is generally defined as a raised blood pressure exceeding 140/ 90 mmHg, divided into two types: ● Essential (or primary) hypertension: accounts for 95% of cases and is where no secondary cause is identified. ● Secondary hypertension: the result of an underlying disease (e.g. renal, pulmonary, endocrine, or drug/ toxin). Pre- HTN is defined as systolic BP (SBP) 120– 139 mmHg and diastolic BP (DBP) 80– 89 mmHg. BP is the product of cardiac output (heart stroke volume and heart rate) and the total peripheral resistance of ves­sels supplied by the heart. Thus, three main systems are responsible for generating BP: the heart (pumping pres­sure), vessel tone (being the systemic resistance), and the kidney (regulating intravascular volume). Three main physiological systems regulate heart, ves­sels, and kidney with respect to blood pressure: 1. The sympathetic nervous system: changes in BP are sensed by a feedback mechanism mediated by baro­receptors in the walls of the aortic arch and carotid sinuses. Increasing BP causes firing of glossopha­ryngeal and vagus nerves, inhibiting sympathetic outflow via the medulla (tractus solitarius). This, in turn, leads to parasympathetic dominance and a reduction in peripheral resistance (vasodilation through β1- adrenoceptors) and cardiac output (by reduced heart rate and reduced contractility through α1- adrenoceptors). Centrally acting antihypertensive drugs act at the nucleus tractus solitarius (e.g. clonidine/ methyldopa) or ventrolateral medulla (e.g. moxonidine). 2. The renin- angiotensin- aldosterone system: this system regulates blood volume and systemic vascular resistance, thus influencing cardiac output and arterial pressure. This feedback mechanism starts in the kidney with the release of renin into the peripheral circula­tion. Renin release, from juxtaglomerular cells (JC), is stimulated by sympathetic mechanisms (involving α1- receptors on JC themselves), decreased afferent ar­teriole pressure (from systemic hypotension or renal artery stenosis) or declining Na<sup>+</sup> levels in the distal tu­bules of the kidney. Prostaglandins, such as PGE2 and PGI2 (prostacyclin), also cause release of renin sec­ondary to reduced NaCl transport in the macular densa (see Topic 5.2 ‘Acute kidney injury’).

Abstract 18266: Overactive Tgfβ Signaling in Smooth Muscle Cells Induces Hypertension in Mice Through Increased Myogenic Tone and is Responsible for Increased Myogenic Tone in Resistance Vessels of Hypertensive Patients

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Daniela Carnevale ◽  
Manuel Casaburo ◽  
Dario Bizzotto ◽  
Daniela Cugino ◽  
Giulio Selvetella ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Peripheral Resistance ◽  
Myogenic Tone ◽  
Resistance Arteries ◽  
Tgfβ Signaling ◽  
Hypertensive Patients ◽  
Resistance Vessels ◽  
Human Pathology

Emilin1 (E1) is a protein of the extracellular matrix that regulates TGFβ activity through proteolysis of the proTGFβ. E1 KO mice are hypertensive, with increased TGFβ activation. As E1 is expressed in blood vessels starting from embryonic life to adulthood, is still unknown whether the E1 KO phenotype results from a developmental defect or lack of a homeostatic role exerted in the adult. To dissect this issue, we inactivated E1 in smooth muscle cells (VSMCs) of adult mice, by the use of floxed E1 and CreERT2 [a tamoxifen (TAM) inducible Cre recombinase] under the control of the smooth muscle myosin heavy chain (Smmhc) promoter. When Smmhc-CreERT2 E1fl/fl mice were given TAM, blood pressure significantly increased (124±1 vs basal condition 106±1 mmHg) as well as myogenic response in resistance arteries (16.3±0.7 vs basal condition 11.4±0.1 % at 125 mmHg). In order to evaluate the relevance of our findings in the human pathology, we enrolled 20 hypertensive and 20 normotensive patients that underwent neurosurgical intervention for primary lumbar hernia repair and dissected out resistance vessels from skeletal muscle biopsies. We analyzed the myogenic tone of human peripheral resistance vessels in a pressure myograph and randomized vessels to receive vehicle, a neutralizing antibody anti-TGFβ or a preimmune non relevant IgG. As first, we found that hypertensive patients had significantly increased myogenic tone as compared to normotensive (16.6±2.1% vs 10.5±0.4% at 125 mmHg). Moreover, the pretreatment of vessels with anti-TGFβ antibody normalized the myogenic tone of hypertensive patients (10.8±0.6%) to the levels of normotensives (11.8±1.3%). A pretreatment with the non relevant IgG did not modify the myogenic tone of hypertensives (17±0.6%), thus demonstrating that the effect was dependent of an increased TGFβ signaling in vessels of hypertensive patients. Overall, our results suggest that the TGFβ pathway in VSMC, is crucial for the myogenic tone of resistance arteries and is linked to the regulation of blood pressure. The data obtained in peripheral resistance vessels from hypertensive patients, that display an increased myogenic tone dependent on overactive TGFβ signaling, highlight the translational potential of our findings to the human pathology.

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