Vascular Reactivity in the Pathogenesis of Spontaneous Hypertension

1. Alterations in vascular reactivity were assessed in isolated artificially perfused kidneys from stroke-prone spontaneously hypertensive (spSH) rats at different stages of hypertension and after neonatal sympathectomy with 6-hydroxydopamine (6-OHDA). 2. During the pre-hypertensive stage, and the early and chronic stages of hypertension, the responses to noradrenaline, vasopressin, serotonin and angiotensin II were enhanced in renal vascular beds from spSH animals compared with age- and sex-matched Wistar—Kyoto (WK) rats; dose—response curves were shifted to the left, had steeper slopes, greater maximal responses and decreased thresholds. 3. With increasing severity and duration of hypertension, renal vascular resistance at maximal vasodilatation increased, the slopes of the dose-response curves were steeper and maximal responses were greater. 4. Neonatal sympathectomy with 6-OHDA greatly attenuated but did not prevent the eventual development of hypertension; furthermore, this treatment had no effect on the enhanced resistance or reactivity in renal vascular beds from spSH rats. 5. The appearance of enhanced resistance and reactivity in the early stages of hypertension and the inability to prevent these vascular changes by neonatal sympathectomy suggest that these alterations are a primary pathogenic mechanism in spSH rats.

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Acute Effects of Triiodothyronine on Endothelial Function in Human Subjects

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-1552 ◽

2007 ◽

Vol 92 (1) ◽

pp. 250-254 ◽

Cited By ~ 29

Author(s):

Raffaele Napoli ◽

Vincenzo Guardasole ◽

Valentina Angelini ◽

Emanuela Zarra ◽

Daniela Terracciano ◽

...

Keyword(s):

Endothelial Function ◽

Dose Response ◽

Vascular Reactivity ◽

Controlled Trial ◽

University Hospital ◽

Acute Effects ◽

Response Curves ◽

Double Blind ◽

Low T3 ◽

Dose Response Curves

Abstract Context: Thyroid hormone regulates several cardiovascular functions, and low T3 levels are frequently associated with cardiovascular diseases. Whether T3 exerts any acute and direct effect on endothelial function in humans is unknown. Objective: Our objective was to clarify whether acute changes in serum T3 concentration affect endothelial function. Design, Setting, and Subjects: Ten healthy subjects (age, 24 ± 1 yr) participated in a double-blind, placebo-controlled trial at a university hospital. Interventions: T3 (or placebo) was infused for 7 h into the brachial artery to raise local T3 to levels observed in moderate hyperthyroidism. Vascular reactivity was tested by intraarterial infusion of vasoactive agents. Main Outcome Measures: We assessed changes in forearm blood flow (FBF) measured by plethysmography. Results: FBF response to the endothelium-dependent vasodilator acetylcholine was enhanced by T3 (P = 0.002 for the interaction between T3 and acetylcholine). The slopes of the dose-response curves were 0.41 ± 0.06 and 0.23 ± 0.04 ml/dl·min/μg in the T3 and placebo study, respectively (P = 0.03). T3 infusion had no effect on the FBF response to sodium nitroprusside. T3 potentiated the vasoconstrictor response to norepinephrine (P = 0.006 for the interaction). Also, the slopes of the dose-response curves were affected by T3 (1.95 ± 0.77 and 3.83 ± 0.35 ml/dl·min/mg in the placebo and T3 study, respectively; P < 0.05). The increase in basal FBF induced by T3 was inhibited by NG-monomethyl-l-arginine. Conclusions: T3 exerts direct and acute effects on the resistance vessels by enhancing endothelial function and norepinephrine-induced vasoconstriction. The data may help clarify the vascular impact of the low T3 syndrome and point to potential therapeutic strategies.

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Alterations in renal vascular resistance and reactivity in spontaneous hypertension of rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1980.238.3.h287 ◽

1980 ◽

Vol 238 (3) ◽

pp. H287-H293 ◽

Cited By ~ 10

Author(s):

K. H. Berecek ◽

U. Schwertschlag ◽

F. Gross

Keyword(s):

Vascular Resistance ◽

Dose Response ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Response Curves ◽

Renal Vasculature ◽

Spontaneously Hypertensive ◽

Wky Rats ◽

Dose Response Curves ◽

Renal Vascular

Vascular resistance and reactivity were investigated in isolated, constant flow perfused kidneys of stroke-prone spontaneously hypertensive rats (SHRSP) and age- and sex-matched normotensive Wistar-Kyoto control rats (WKY rats). Stroke-prone spontaneously hypertensive rats were studied at 4 wk, 2 mo, and 4 mo of age representing different stages of development of hypertension. Resistance in maximally vasodilated vascular beds was greater and the pressure-flow relationship was significantly shifted to the left in kidneys of SHRSP as compared to WKY rats. Responses to norepinephrine, vasopressin, serotonin, and angiotensin II were enhanced in the renal vascular bed of SHRSP. Dose-response curves were shifted to the left, had steeper slopes, decreased thresholds, and increased maximal responses. With longer duration of hypertension, resistance increased, the slopes of the dose-response curves were steeper, and maximum responses greater. The higher resistance and enhanced reactivity in the renal vasculature of SHRSP, already demonstrable in the prehypertensive stage appear to be due to primary structural and functional alterations of the resistance vessels.

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Modification of vasodilator response in streptozotocin-induced diabetic rat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y99-106 ◽

1999 ◽

Vol 77 (12) ◽

pp. 980-985 ◽

Cited By ~ 13

Author(s):

Jean-François Bouchard ◽

Éric C Dumont ◽

Daniel Lamontagne

Keyword(s):

Diabetes Mellitus ◽

Adenylyl Cyclase ◽

Dose Response ◽

Vascular Reactivity ◽

Diabetic Rats ◽

Diabetic Rat ◽

Response Curves ◽

Experimental Conditions ◽

Isolated Hearts ◽

Dose Response Curves

Functional dilatory response in streptozotocin-induced diabetic rats was investigated using thoracic aortas, isolated hearts, and mesenteric beds. Dose-response curves to the PGI2 analogue iloprost on phenylephrine-preconstricted rings of diabetic rats and controls were comparable. In contrast, decreased vasodilation in diabetic rats was observed when dose-response curves to iloprost were performed in hearts and on phenylephrine-preconstricted mesenteric beds. Dose-response curves to forskolin, an adenylyl cyclase activator, performed with hearts and phenylephrine-preconstricted aortic rings and isolated mesenteric beds of diabetic rats and controls were comparable. However, a decreased vasodilation to the ATP-sensitive potassium channel (KATP) activator lemakalim was observed in diabetic hearts, but not in aortic rings and mesenteric beds. In conclusion, under our experimental conditions, diabetes mellitus affects the vasodilation to iloprost in both coronary and mesenteric beds, but not in the aorta. In the heart, this modification of vascular reactivity may be due to a decrease in KATP channel mediated response and not to a decreased activity of adenylyl cyclase. At this time, in the isolated mesenteric bed, the mechanism of this modification in vascular reactivity remains unknown.Key words: diabetes mellitus, iloprost, KATP channels, adenylyl cyclase, aorta, coronary circulation, mesenteric bed.

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Nifedipine-sensitive vascular reactivity of femoral arteries in WKY: the effect of pertussis toxin pretreatment and endothelium removal

Physiological Research ◽

10.33549/physiolres.931367 ◽

2007 ◽

pp. 663-666

Author(s):

S Líšková ◽

J Kuneš ◽

J Zicha

Keyword(s):

G Proteins ◽

Pertussis Toxin ◽

Dose Response ◽

Vascular Reactivity ◽

Response Curves ◽

Femoral Arteries ◽

Voltage Dependent ◽

Dose Response Curves ◽

Vasodilator Action ◽

The Right

Maintenance of norepinephrine (NE)-induced contraction is dependent on Ca(2+) influx through L-type voltage-dependent Ca(2+) channels (VDCC), which is opposed by nitric oxide. Adrenergic receptors are coupled with different G proteins, including inhibitory G proteins (Gi) that can be inactivated by pertussis toxin (PTX). Our study was aimed to investigate the effects of endothelium removal, PTX pretreatment and acute VDCC blockade by nifedipine on the contractions of femoral arteries stimulated by norepinephrine. We used 12-week-old male WKY, half of the rats being injected with PTX (10 microg/kg i.v., 48 h before the experiment), which considerably reduced their blood pressure (BP). Contractions of isolated arteries were measured using Mulvany-Halpern myograph. NE dose-response curves determined in femoral arteries from PTX-treated WKY rats were shifted to the right compared to those from control WKY. On the contrary, removal of endothelium augmented NE dose-response curves shifting them to the left. Acute VDCC blockade by nifedipine (10(-7) M) abolished all differences in NE dose-response curves which were dependent on the presence of either intact endothelium or functional Gi proteins because all NE dose-response curves were identical to the curve seen in vessels with intact endothelium from PTX-treated animals. We can conclude that BP reduction after PTX injection is accompanied by the attenuation of NE-induced contraction of femoral arteries irrespective of endothelium presence. Moreover, our data indicate that both vasodilator action of endothelium and Gi-dependent vasoconstrictor effect of norepinephrine operate via the control of Ca(2+) influx through VDCC.

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Pulmonary vascular reactivity after repetitive exposure to selected biogenic amines

Journal of Applied Physiology ◽

10.1152/jappl.1983.55.6.1868 ◽

1983 ◽

Vol 55 (6) ◽

pp. 1868-1876 ◽

Cited By ~ 6

Author(s):

M. Cutaia ◽

R. J. Porcelli

Keyword(s):

Biogenic Amines ◽

Dose Response ◽

Vascular Reactivity ◽

Lower Lobe ◽

Left Lower Lobe ◽

Base Line ◽

Response Curves ◽

Arterial Blood ◽

Repetitive Exposure ◽

Dose Response Curves

The present study investigated the effects of repetitive exposure to a select group of biogenic amines (epinephrine, norepinephrine, histamine, and serotonin) on pulmonary vascular reactivity by constructing and analyzing a set of four sequential cumulative dose-response curves to one biogenic amine in the isolated blood-perfused left lower lobe of the cat lung in vivo. The dose-response curves were obtained under conditions of constant flow, insuring that the observed pressure changes in the lobe were pressor responses resulting from vasoconstriction rather than flow-related changes. Histamine and epinephrine demonstrated a progressive loss of initial vasoconstrictor activity, whereas the responses to serotonin remained unchanged after repetitive exposure. Norepinephrine demonstrated two different patterns of response, depending on the dose range employed; norepinephrine (0.068-2.27 nmol/ml) demonstrated a loss of the original vasoconstrictor activity, in a pattern similar to histamine and epinephrine, while higher doses of norepinephrine (0.34-9.1 nmol/ml) demonstrated no change in activity with a left shift in the concentration at which the maximal responses occurred, suggesting an increase in sensitivity as a result of repeated exposure. These results were obtained in the absence of significant alterations of arterial blood gases, changes in base-line tone in the experimental left lower lobe, or the development of severe pulmonary edema. These data suggest that only the agents that are capable of stimulating antagonistic vasoconstrictor and vasodilator receptors demonstrated a loss of pulmonary vasoconstrictor activity, which may result from a functional shift in the balance of antagonistic receptor activity with continued exposure.

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Dose-response curves of the uterine and placental vascular beds to prostaglandin I2

American Journal of Obstetrics and Gynecology ◽

10.1016/0002-9378(88)90558-3 ◽

1988 ◽

Vol 159 (6) ◽

pp. 1372-1375 ◽

Cited By ~ 11

Author(s):

Mark C. Hollister ◽

Deborah L. Reid ◽

Terrance M. Phernetton ◽

Megan Landauier ◽

John H.G. Rankin

Keyword(s):

Dose Response ◽

Prostaglandin I2 ◽

Response Curves ◽

Vascular Beds ◽

Dose Response Curves

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Dose-response Curves in the Fibrin Plate Assay Fibrinolytic Activity of Proteases

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647705 ◽

1974 ◽

Vol 32 (02/03) ◽

pp. 356-365 ◽

Cited By ~ 12

Author(s):

F Haverkate ◽

D. W Traas

Keyword(s):

Dose Response ◽

Fibrinolytic Activity ◽

Enzyme Concentration ◽

Response Curves ◽

Agar Gel ◽

Porcine Tissue ◽

Plate Assay ◽

Fibrin Plate ◽

Different Types ◽

Dose Response Curves

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.

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BIOASSAY OF THYROID HORMONE USING HYPOTHYROID TADPOLES

Acta Endocrinologica ◽

10.1530/acta.0.0410143 ◽

1962 ◽

Vol 41 (1) ◽

pp. 143-153 ◽

Cited By ~ 2

Author(s):

U. Henriques

Keyword(s):

Thyroid Hormone ◽

Dose Response ◽

Developmental Rate ◽

Response Curves ◽

Sodium Salts ◽

Dose Response Curves

ABSTRACT A bioassay of thyroid hormone has been developed using Xenopus larvae made hypothyroid by the administration of thiourea. Only tadpoles of uniform developmental rate were used. Thiourea was given just before the metamorphotic climax in concentrations that produced neoteni in an early metamorphotic stage. During maintained thiourea neotoni, 1-thyroxine and 1-triiodothyronine were added as sodium salts to the water for three days and at the end of one week the stage of metamorphosis produced was determined. In this way identical dose-response curves were obtained for the two compounds. No qualitative differences between their effects were noted except that triiodothyronine seemed more toxic than thyroxine in equivalent doses. Triiodothyronine was found to be 7–12 times as active as thyroxine.

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