Vascular reactivity during the development of two-kidney, one-clip Goldblatt hypertension in conscious dogs

1982 ◽  
Vol 60 (12) ◽  
pp. 1482-1492 ◽  
Author(s):  
Stan Greenberg ◽  
Claude McGowan ◽  
Monica Gaida
Keyword(s):  
Vascular Reactivity ◽  
Peripheral Resistance ◽  
Vascular Wall ◽  
Conscious Dogs ◽  
Ang Ii ◽  
Intrinsic Factors ◽  
Pressor Responses ◽  
Pressure Changes ◽  
Goldblatt Hypertension

This study evaluates the sequential changes in vascular reactivity in conscious dogs during the early and late phases of two-kidney, one-clip Goldblatt hypertension (2-KGH) produced by unilateral renal artery constriction (URAC). The in vivo responses to serotonin (5-HT), norepinephrine (NE), angiotensin II (Ang II), prostacyclin (PGI2), acetylcholine (ACH), and nitroglycerin (GTN) were reproducible and stable throughout the 32-day period of study in dogs subjected to sham URAC. The vascular responses to 5-HT, Ang II, and PGI2 were enhanced day 1 post-URAC, before mean arterial pressure (MAP), cardiac output (CO), or total peripheral resistance (TPR) increased. The magnitude of the enhanced reactivity progressed on days 4 and 32 post-URAC, as hypertension developed. The pressor responses to NE did not change from pre-URAC values until CO and MAP were elevated. The vasodepressor responses to ACH and GTN diminished over a 12-day period post-URAC, in parallel with the change in CO, but prior to any increase in TPR. These data suggest that in dogs with 2-KGH changes in vascular reactivity precede the development of the increased MAP and TPR of hypertension. The lack of uniformity of the onset of the reactivity changes to the different agonists suggests that both intrinsic factors and pressure changes modify the vascular wall in the early and later stages of 2-KGH.

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.

Acute and long-term TNF-alpha administration increases pulmonary vascular reactivity in isolated rat lungs

1992 ◽  
Vol 73 (2) ◽  
pp. 708-712 ◽  
Author(s):  
T. Stevens ◽  
P. L. Janssen ◽  
A. Tucker
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Reactivity ◽  
Acute Hypoxia ◽  
Tnf Alpha ◽  
Ang Ii ◽  
Necrosis Factor Alpha ◽  
Arterial Hypoxemia ◽  
Pressor Responses

Tumor necrosis factor-alpha (TNF-alpha) causes pulmonary hypertension and arterial hypoxemia, but the mechanisms are unknown. We conducted two experiments to test the hypothesis that TNF-alpha alters pulmonary vascular reactivity, which in turn could cause either pulmonary hypertension or arterial hypoxemia. In experiment 1, rats were given acute or long-term injections of TNF-alpha (recombinant human) in vivo. Rats treated acutely received either saline or TNF-alpha (40 micrograms/kg iv in saline) 3 min (TNF-3 min; n = 8), 20 min (TNF-20 min; n = 8), or 24 h (TNF-24 h; n = 5) before the lungs were isolated. Rats treated chronically received injections of either saline or TNF-alpha (250 micrograms/kg ip in saline) two times per day for 7 days (TNF-7 days; n = 9). Lungs were isolated and perfused with Earle's salt solution (+2 g/l NaHCO3 + 4 g/100 ml Ficoll), and vascular reactivity was tested with acute hypoxia (3 min; 3% O2) and angiotensin II (ANG II; 0.025–0.40 micrograms). Pulmonary pressor responses to hypoxia were greater (P less than 0.05) in TNF-20 min and TNF-7 day groups. ANG II responses were increased (P less than 0.05) in TNF-7 day rats. In experiment 2, lungs were isolated and perfused and received direct pulmonary arterial injections of TNF-alpha (0.2, 2.0, and 20 micrograms) or saline, after stable responses to hypoxia and ANG II (0.10 microgram) were attained. Reactivity was not different between control and TNF-alpha rats before the injections, but TNF-alpha increased (P less than 0.05) responses to hypoxia and ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased alpha 1-adrenergic vascular sensitivity during development of hypertension in conscious dogs

1993 ◽  
Vol 264 (4) ◽  
pp. H1259-H1268 ◽  
Author(s):  
N. Uemura ◽  
D. E. Vatner ◽  
Y. T. Shen ◽  
J. Wang ◽  
S. F. Vatner
Keyword(s):  
Adrenergic Receptor ◽  
Peripheral Resistance ◽  
Aortic Pressure ◽  
Conscious Dogs ◽  
Aortic Tissue ◽  
Ang Ii ◽  
Receptor Density ◽  
Adrenergic Stimulation ◽  
Before And After ◽  
Vascular Responsiveness

The goal of this study was to determine whether enhanced vascular responsiveness during the development of perinephritic hypertension is selective or nonspecific. The effects of graded infusions of norepinephrine (NE), phenylephrine (PE), angiotensin II (ANG II), and vasopressin (VP) were examined on mean arterial pressure, total peripheral resistance (TPR), and aortic pressure-diameter relationships in conscious dogs. NE increased TPR significantly greater (P < 0.01) in hypertension than normotension, as did PE infusion, whereas ANG II and VP increased TPR similarly before and after hypertension. Analysis of aortic pressure-diameter relationships also demonstrated significant (P < 0.05) shifts in response to NE and PE, but not ANG II and VP, during the development of hypertension. In normotensive dogs, low doses of ANG II infusion also enhanced the vasoconstrictor response not only to NE and PE but also to VP. In contrast to what was observed in hypertension, in the presence of ANG II infusion after ganglionic blockade, enhanced responses to PE and NE were no longer observed. The alpha 1-adrenergic receptor density in membrane preparations from aortic tissue, as determined by [3H]prazosin binding, was higher (P < 0.05) in hypertensive dogs than control dogs. Thus the vascular responsiveness in the aorta and resistance vessels is enhanced to alpha 1-adrenergic stimulation, but not to all vasoconstrictors, during developing perinephritic hypertension. The mechanism appears to involve increased alpha 1-adrenergic receptor density.

ANG II increases TIMP-1 expression in rat aortic smooth muscle cells in vivo

2003 ◽  
Vol 284 (2) ◽  
pp. H635-H643 ◽  
Author(s):  
Giovanna Castoldi ◽  
Cira R. T. di Gioia ◽  
Federico Pieruzzi ◽  
Cristina D'Orlando ◽  
Willy M. M. van de Greef ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Vascular Wall ◽  
Dependent Manner ◽  
Ang Ii ◽  
Maximal Increase ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in tissue remodeling processes. TIMP-1 is the main native inhibitor of MMPs and it contributes to the development of tissue fibrosis. It is known that ANG II plays a fundamental role in vascular remodeling. In this study, we investigated whether ANG II modulates TIMP-1 expression in rat aortic smooth muscle cells. In vitro, ANG II induces TIMP-1 mRNA expression in a dose-dependent manner. The maximal increase in TIMP-1 expression was present after 3 h of ANG II stimulation. The ANG II increase in TIMP-1 expression was mediated by the ANG type 1 receptors because it was blocked by losartan. The increase in TIMP-1 expression was present after the first ANG II treatment, whereas repeated treatments (3 and 5 times) did not modify TIMP-1 expression. In vivo, exogenous ANG II was administered to Sprague-Dawley rats (200 ng · kg−1· min−1sc) for 6 and 25 days. Control rats received physiological saline. After treatment, systolic blood pressure was significantly higher ( P < 0.01), whereas plasma renin activity was suppressed ( P < 0.01), in ANG II-treated rats. ANG II increased TIMP-1 expression in the aorta of ANG II-treated rats both at the mRNA ( P < 0.05) and protein levels as evaluated by Western blotting ( P < 0.05) and/or immunohistochemistry. Neither histological modifications at the vascular wall nor differences in collagen content in the tunica media were present in both the ANG II- and saline-treated groups. Our data demonstrate that ANG II increases TIMP-1 expression in rat aortic smooth muscle cells. In vivo, both short- and long-term chronic ANG II treatments increase TIMP-1 expression in the rat aorta. TIMP-1 induction by ANG II in aortic smooth muscle cells occurs in the absence of histological changes at the vascular wall.

Platelet-activating factor antagonists increase vascular reactivity in perfused rat lungs

1988 ◽  
Vol 65 (5) ◽  
pp. 1921-1928 ◽  
Author(s):  
J. Haynes ◽  
S. W. Chang ◽  
K. G. Morris ◽  
N. F. Voelkel
Keyword(s):  
Pulmonary Circulation ◽  
Vascular Reactivity ◽  
Platelet Activating Factor ◽  
Base Line ◽  
Ang Ii ◽  
Rat Lungs ◽  
Hypoxic Vasoconstriction ◽  
Paf Receptor ◽  
Blood Elements

Platelet-activating factor (PAF) administered to the pulmonary circulation in low dose (nanogram) has vasodilatory properties. Therefore, we investigated whether endogenous PAF plays a role in the control of tone in the pulmonary circulation. The PAF receptor antagonists, SRI 63-441 (2.6 X 10(-4) M) and L659,989 (1 X 10(-5) M), were the major investigative tools. In isolated perfused rat lungs, both agents caused a persistent increase in base-line perfusion pressure (Ppa), potentiated angiotensin II (ANG II) vasoconstriction, and potentiated hypoxic vasoconstriction (HPV). This potentiation of ANG II and HPV was found to be independent of circulating blood elements. Vasodilation in the presence of PAF blockade was also impaired. The combination of cyclooxygenase inhibition and PAF receptor blockade had an additive effect on ANG II vasoconstriction but did not cause more potentiation of HPV than achieved with PAF antagonism alone. In vivo, SRI 63-441 (10 mg/kg) caused only a transient increase in base-line Ppa without altering ANG II and hypoxic vasoconstriction. These findings support a vasodilatory role for endogenous PAF in the pulmonary circulation.

Effects of indomethacin, during pregnancy in the rat, on responses to noradrenaline and angiotensin II in vivo, and responses to phenylephrine in vitro

1990 ◽  
Vol 2 (5) ◽  
pp. 587 ◽  
Author(s):  
C Jansakul ◽  
RG King ◽  
AL Boura
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Plasma Volume ◽  
Ang Ii ◽  
Pregnant Rats ◽  
Prostaglandin Production ◽  
Pressor Responses

Pressor responses to both angiotensin II (Ang II) and noradrenaline (NA) were reduced in 20-day-pregnant rats compared with those in non-pregnant animals, regardless of whether the results were expressed in terms of the dose per kilogram of body weight or per millilitre of estimated plasma volume. Inhibition of prostaglandin production with indomethacin (10 mg kg-1, i.v.) was not accompanied by any significant effect on responses to Ang II in either non-pregnant or 20-day-pregnant animals. However, it attenuated the effects of NA in 20-day-pregnant rats. Indomethacin (10(-5) or 3 x 10(-5) M) did not potentiate in vitro vasoconstrictor responses to phenylephrine of endothelium-intact or -denuded thoracic aortic rings from non-pregnant or 20-day-pregnant rats. These results suggest that subsensitivity to Ang II or NA during pregnancy in the rat is not due to dilution of the dose of these autacoids resulting from increased plasma volume, nor to an increased output of vasodilator prostaglandins.

Effect of pioglitazone on vascular reactivity in vivo and in vitro

1996 ◽  
Vol 270 (3) ◽  
pp. R660-R666 ◽  
Author(s):  
T. A. Kotchen ◽  
H. Y. Zhang ◽  
S. Reddy ◽  
R. G. Hoffmann
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Sprague Dawley ◽  
Vasoactive Agents ◽  
Sprague Dawley Rats ◽  
Pressor Responses

Pioglitazone (a thiazolidinedione derivative) increases insulin sensitivity and prevents hypertension in the Dahl-salt-sensitive (S) rat. The present study was undertaken to determine if pioglitazone modulates pressor responsiveness to vasoactive agents, both in vivo and in vitro. In vivo, pretreatment with pioglitazone inhibited (P < 0.02) pressor responses to both norepinephrine and angiotensin II in conscious Dahl-S, but not in Sprague-Dawley rats. In vitro, pioglitazone augmented the capacity of insulin to inhibit pressor responses of strips of thoracic aortas to norepinephrine, but not to angiotensin. Additionally, in vitro, incubation with insulin plus pioglitazone augmented acetylcholine-induced, but not nitroprusside-induced vasodilation. Pioglitazone pretreatment increased (P < 0.001) in vitro insulin-stimulated glucose uptake in adipose tissue, but not in thoracic aortas of Dahl-S. We hypothesize that pioglitazone attenuates hypertension by modulating the effects of insulin on vascular function, resulting in both blunted vasoconstriction and augmented acetylcholine-induced vasodilation. These alterations are not accounted for by an effect of pioglitazone on glucose uptake by vascular smooth muscle.

Cardiovascular actions of vasopressin: baroreflex modulation in the conscious rat

1986 ◽  
Vol 251 (6) ◽  
pp. H1244-H1251 ◽  
Author(s):  
R. L. Webb ◽  
J. W. Osborn ◽  
A. W. Cowley
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Peripheral Resistance ◽  
Base Line ◽  
Ang Ii ◽  
Response Curves ◽  
Conscious Rat ◽  
Cardiovascular Actions ◽  
Pressor Responses ◽  
Baroreceptor Reflexes

Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were recorded during graded infusions of arginine vasopressin (AVP), angiotensin II (ANG II), and phenylephrine (PE) in conscious, unrestrained, sinoaortic-denervated (SAD) and normal rats. Base-line MAP, CO, and TPR values before infusion were not different between groups. HR values were significantly higher in SAD rats. Dose-response curves indicated that there was a similar enhancement in pressor sensitivity to AVP, ANG II, and PE in the absence of the baroreceptors. Pressor responses to AVP were buffered by offsetting decreases of CO. Similar elevations in MAP evoked a 50% greater reduction in CO with AVP, and HR decreased 1.5 times as much with AVP than with ANG II or PE. The dose of AVP required to raise MAP by 25 mmHg in control rats resulted in similar falls of CO in SAD rats, whereas HR responses to AVP were attenuated significantly in SAD rats. We conclude that baroreceptor buffering of AVP-induced pressor responses is due principally to reflex reduction of TPR. Furthermore, CO suppression was not baroreflex-mediated, whereas bradycardia was reflex dependent. Finally, in rats, AVP does not appear to interact with the baroreceptor reflexes in a manner unique from other vasoconstrictor agents to buffer MAP.

scholarly journals KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine

2016 ◽  
Vol 310 (6) ◽  
pp. H693-H704 ◽  
Author(s):  
Adam G. Goodwill ◽  
Lijuan Fu ◽  
Jillian N. Noblet ◽  
Eli D. Casalini ◽  
Daniel Sassoon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Vascular Reactivity ◽  
Ex Vivo ◽  
Vascular Wall ◽  
Kv7 Channels ◽  
Endothelial Denudation ◽  
Voltage Dependent

Hydrogen peroxide (H2O2) and voltage-dependent K+ (KV) channels play key roles in regulating coronary blood flow in response to metabolic, ischemic, and paracrine stimuli. The KV channels responsible have not been identified, but KV7 channels are possible candidates. Existing data regarding KV7 channel function in the coronary circulation (limited to ex vivo assessments) are mixed. Thus we examined the hypothesis that KV7 channels are present in cells of the coronary vascular wall and regulate vasodilation in swine. We performed a variety of molecular, biochemical, and functional (in vivo and ex vivo) studies. Coronary arteries expressed KCNQ genes (quantitative PCR) and KV7.4 protein (Western blot). Immunostaining demonstrated KV7.4 expression in conduit and resistance vessels, perhaps most prominently in the endothelial and adventitial layers. Flupirtine, a KV7 opener, relaxed coronary artery rings, and this was attenuated by linopirdine, a KV7 blocker. Endothelial denudation inhibited the flupirtine-induced and linopirdine-sensitive relaxation of coronary artery rings. Moreover, linopirdine diminished bradykinin-induced endothelial-dependent relaxation of coronary artery rings. There was no effect of intracoronary flupirtine or linopirdine on coronary blood flow at the resting heart rate in vivo. Linopirdine had no effect on coronary vasodilation in vivo elicited by ischemia, H2O2, or tachycardia. However, bradykinin increased coronary blood flow in vivo, and this was attenuated by linopirdine. These data indicate that KV7 channels are expressed in some coronary cell type(s) and influence endothelial function. Other physiological functions of coronary vascular KV7 channels remain unclear, but they do appear to contribute to endothelium-dependent responses to paracrine stimuli.

Central ANP administration in conscious dogs responding to dehydration and hypovolemia

1992 ◽  
Vol 262 (5) ◽  
pp. R746-R753 ◽  
Author(s):  
E. Szczepanska-Sadowska ◽  
C. S. Oppermann ◽  
E. Simon ◽  
D. A. Gray ◽  
K. Pleschka ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Fluid ◽  
High Performance ◽  
Pressure Control ◽  
Blood Parameters ◽  
Conscious Dogs ◽  
Plasma Norepinephrine ◽  
Ang Ii ◽  
Time Control ◽  
Pressure Changes

Eighteen beagles were chronically instrumented with an anterior third ventricular (A3V) infusion device to analyze, in conscious dogs, the involvement of central atrial natriuretic peptide (ANP) in body fluid and blood pressure control. The dogs' osmotic and body fluid homeostasis was challenged by 24 h water deprivation or blood withdrawal (12 ml/kg body wt) to elucidate possible modifying influences on the release of arginine vasopressin (AVP), angiotensin II (ANG II), and drinking. Three series of experiments were performed: 1) infusion of ANP (500 ng/min) dissolved in artificial cerebrospinal fluid (aCSF) and given for 10 min, 2) infusion of aCSF alone for the same length of time, and 3) time control experiments without infusion. Plasma AVP and ANG II were analyzed by radioimmunoassay, and in several experiments on dehydrated dogs, plasma norepinephrine and epinephrine were additionally determined by high-performance liquid chromatography. Various blood parameters and rectal and ear skin temperatures were measured. Arterial pressure and heart rate were recorded in three animals additionally equipped with carotid loops. Changes in plasma AVP and ANG II induced by dehydration and bleeding were not significantly modified by A3V infusions of ANP and aCSF in comparison to time controls. Blood pressure changes were similar in experiments with A3V ANP infusion and time controls during bleeding and reinfusion. It is concluded that central ANP is not important in the control of vasopressin and renin-angiotensin systems during osmotic and volume challenges in conscious dogs.

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