Forearm vasoconstriction to endothelin-1 is impaired, but constriction to sarafotoxin 6c and vasodilatation to BQ-123 unaltered, in patients with essential hypertension

2002 ◽  
Vol 103 (s2002) ◽  
pp. 53S-58S ◽  
Author(s):  
Charles J. FERRO ◽  
William G. HAYNES ◽  
Malcolm F. HAND ◽  
David J. WEBB
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Essential Hypertension ◽  
Receptor Agonist ◽  
Forearm Blood Flow ◽  
Hypertensive Patients ◽  
Control Subjects ◽  
Eta Receptor ◽  
Etb Receptor ◽  
And Control

The importance of endothelin-1 (ET-1) in the pathophysiology of essential hypertension is unclear. We therefore compared the effects of endothelin ETA receptor blockade and the stimulation of ETA and ETB receptors, and their interaction with the sympathetic nervous system, in the forearm resistance vessels of patients with essential hypertension and healthy control subjects. A total of 27 untreated patients with essential hypertension (blood pressure >160/100mmHg) and 25 normotensive (blood pressure <140/90mmHg) age- and sex-matched control subjects participated in these studies. A total of 10 patients and 10 controls took part in each phase. Locally active doses of study drugs were infused into the non-dominant brachial artery, while forearm blood flow was measured by venous occlusion plethysmography. A 60min infusion of BQ-123 (an ETA receptor antagonist; 100nmol/min) significantly increased forearm blood flow by 40±8% in hypertensive patients and by 35±5% in controls, with no difference between groups (P = 0.49). Forearm vasoconstriction to ET-1 (an ETA and ETB receptor agonist; 5 pmol/min) for 90min was significantly blunted in hypertensive patients (21±4%) compared with control subjects (37±3%; P = 0.0001). Forearm vasoconstriction to sarafotoxin S6c (an ETB receptor agonist; 10 pmol/min) for 90min was similar in hypertensive patients (44±5%) and control subjects (48±4%; P = 0.95). Sympathetically mediated vasoconstriction produced by lower-body negative pressure was not different in hypertensive patients compared with controls, and was not affected by infusion of ET-1 or sarafotoxin S6c. There were no differences in the observed increase in forearm blood flow with a control vasodilator (sodium nitroprusside) or the observed decrease in forearm blood flow with a control vasoconstrictor (noradrenaline) between hypertensive patients and control subjects. BQ-123 produced a significant increase in forearm blood flow in hypertensive patients, consistent with the anti-hypertensive actions of this agent. In conclusion, forearm vasoconstriction to ET-1, but not to sarafotoxin S6c, was reduced in patients with essential hypertension, consistent with possible down-regulation of the ETA receptor in this condition.

Reduced Plasma Renin Activity in Essential Hypertension: Effects of Blood Pressure, Age and Sodium

1976 ◽  
Vol 51 (s3) ◽  
pp. 185s-188s ◽  
Author(s):  
G. W. Thomas ◽  
J. G. G. Ledingham ◽  
L. J. Beilin ◽  
A. N. Stott
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Plasma Renin Activity ◽  
Inverse Relationship ◽  
Plasma Renin ◽  
Renin Activity ◽  
Hypertensive Patients ◽  
Significant Inverse Relationship ◽  
Control Subjects ◽  
And Control

1. Supine plasma renin activity and its responsiveness to erect posture and frusemide were reduced in fifty-one patients with essential hypertension, compared with fifty-one age- and sex-matched control subjects. 2. Twenty-four hour urinary sodium excretion was similar in hypertensive patients and control subjects, but after intravenous frusemide hypertensive patients excreted significantly less sodium. 3. A significant inverse relationship between plasma renin activity and diastolic blood pressure was demonstrated in hypertensive patients and in normotensive control subjects. 4. A significant inverse relationship between plasma renin activity and age, independent of blood pressure, was shown in hypertensive patients and control subjects. 5. It is concluded that the reduced renin values found in essential hypertension are, in part, the result of the elevated blood pressure acting on the kidney.

Forearm vasoconstriction in response to noradrenaline and NG-monomethyl-L-arginine in essential hypertension

1999 ◽  
Vol 97 (3) ◽  
pp. 277-282 ◽  
Author(s):  
Barry J. KNEALE ◽  
Philip J. CHOWIENCZYK ◽  
Sally E. BRETT ◽  
JohnR. COCKCROFT ◽  
James M. RITTER
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Essential Hypertension ◽  
Forearm Blood Flow ◽  
Venous Occlusion ◽  
Control Group ◽  
No Production ◽  
Primary Role ◽  
Consistent Finding ◽  
And Control

A role for abnormal NO production in essential hypertension remains controversial. Blunted vasoconstriction of forearm resistance vasculature in response to NG-monomethyl-⌊-arginine (⌊-NMMA; an inhibitor of NO biosynthesis), relative to the response to noradrenaline, has been reported in hypertensive patients and interpreted as evidence of reduced basal NO biosynthesis. We sought to determine whether reduced sensitivity of forearm vasculature to the vasoconstrictor action of l-NMMA relative to that of noradrenaline is a consistent finding in essential hypertension. We studied a group of patients (n = 32; blood pressure 176±4/102±2 mmHg; means±S.E.M.) and a group of healthy normotensive controls (n = 32; blood pressure 130±2/75±1 mmHg). Noradrenaline (60–240 pmol·min-1) and ⌊-NMMA (1–4 μmol·min-1) were infused into the brachial artery, and forearm blood flow was measured by venous occlusion plethysmography. The effects of each vasoconstrictor were similar in hypertensive and control subjects. The highest dose of l-NMMA reduced forearm blood flow by 0.75±0.12 ml·min-1·dl-1 in the control group and by 0.89±0.10 ml·min-1·dl-1 in the hypertensive group. The study had 90% power (with P = 0.05) to detect a 10% difference in forearm blood flow response between the hypertensive and control groups. We conclude that reduced sensitivity of forearm resistance vasculature to the vasoconstrictor action of l-NMMA is not a universal feature of essential hypertension. This argues against a primary role for reduced basal NO biosynthesis in skeletal muscle resistance vessels in the pathogenesis of essential hypertension.

Cardiovascular and Sympatho-Adrenal Responses to Mental Stress in Primary Hypertension

1993 ◽  
Vol 85 (4) ◽  
pp. 401-409 ◽  
Author(s):  
Madeleine Lindqvist ◽  
Thomas Kahan ◽  
Anders Melcher ◽  
Paul Hjemdahl
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Neuropeptide Y ◽  
Mental Stress ◽  
Forearm Blood Flow ◽  
Primary Hypertension ◽  
Hypertensive Patients ◽  
Control Subjects ◽  
Venous Plasma

1. Eleven untreated men with mild to moderate primary hypertension and 10 normotensive control subjects were studied at rest and during a mental stress test (Stroop colour word conflict test), which has previously been used in studies of hypertensive patients with regard to non-invasive cardiovascular variables and venous plasma catecholamine concentrations. 2. Heart rate, central cardiovascular pressures, cardiac output (thermodilution) and forearm blood flow (strain gauge plethysmography) were determined. Systemic and forearm vascular resistances were calculated. Arterial and venous plasma adrenaline and noradrenaline concentrations were measured by h.p.l.c., and arterial noradrenaline spillover and noradrenaline overflow from the forearm were assessed by isotope methodology ([3H]noradrenaline). Neuropeptide Y-like immunoreactivity was measured by radioimmunoassay. 3. In hypertensive patients heart rate, arterial blood pressure, cardiac output and forearm blood flow increased by 28%, 13%, 37% and 115%, respectively, and forearm and systemic vascular resistances decreased by 48% and 21%, respectively (P <0.001 for all responses), during stress. These responses were not different from those of the control group. 4. Arterial noradrenaline spillover rose by 63% and noradrenaline overflow from the forearm rose by 150% in the hypertensive patients in response to mental stress (P <0.001); no significant group differences could be demonstrated. However, the forearm noradrenaline overflow response to stress tended to be greater in the hypertensive group (P = 0.11). Arterial adrenaline concentrations doubled in both groups (P <0.001). 5. Arterial neuropeptide Y-like immunoreactivity increased slightly and similarly in the two groups (+7% in hypertensive patients and +9% in control subjects, P <0.05 for both) in response to mental stress. No net overflow of neuropeptide-Y-like immunoreactivity could be detected over the forearm. 6. It is concluded that the cardiovascular and sympatho-adrenal responses to mental stress evaluated in this study are similar in hypertensive patients and control subjects. Stress-induced vasodilatation occurs in the forearm despite signs of increased local sympathetic activity, indicating that powerful neurohormonal vasodilator mechanisms are activated by mental stress.

The Antihypertensive and Renal Activities of Potassium Canrenoate are Associated with Increased Renal Prostaglandin Excretion

1989 ◽  
Vol 77 (2) ◽  
pp. 217-222 ◽  
Author(s):  
Sergio Castellani ◽  
Luca Scarti ◽  
Ji Lin Chen ◽  
Attilio Del Rosso ◽  
Marino Carnovali ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Prostaglandin E2 ◽  
Prostaglandin F2α ◽  
Prostaglandin Synthesis ◽  
Double Blind ◽  
Hypertensive Patients ◽  
Control Subjects ◽  
Potassium Canrenoate ◽  
Normotensive Subjects

1. In a double-blind, randomized, cross-over study the effects of potassium canrenoate administration (100 mg twice daily for 10 days orally) on renal prostaglandin synthesis (prostaglandin E2 and prostaglandin F2α) were evaluated in 10 normotensive females and in 10 females with essential hypertension. 2. When compared with normotensive subjects, hypertensive patients in baseline conditions showed a reduced excretion of urinary prostaglandin E2 associated with an excessive prostaglandin F2α production. 3. Potassium canrenoate significantly reduced mean blood pressure in hypertensive patients [from 118.9 ± 8.7 mmHg (1.62 ± 0.12 kPa) to a peak minimum value of 104.7 ± 9.8 mmHg (1.42 ± 0.13 kPa) on the seventh day of treatment; P < 0.01 for the whole period] but not in control subjects [from 88 ± 9.4 mmHg (1.20 ± 0.13 kPa) to 84.3 ± 8.3 mmHg (1.15 ± 0.11 kPa) on the eighth day, NS] even though potassium canrenoate significantly increased sodium excretion in both groups. Renal prostaglandin excretion was affected differently in the two groups: in control subjects excretion of both prostaglandin E2 and prostaglandin F2α was increased after drug administration, whereas in hypertensive patients only prostaglandin E2 excretion was enhanced.

Plasma Catecholamines and Renin Activity in Response to Exercise in Patients with Essential Hypertension

1975 ◽  
Vol 49 (5) ◽  
pp. 511-514
Author(s):  
J. Chodakowska ◽  
K. Nazar ◽  
B. Wocial ◽  
M. Jarecki ◽  
B. Skórka
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Plasma Renin Activity ◽  
Plasma Catecholamines ◽  
Plasma Renin ◽  
Work Load ◽  
Renin Activity ◽  
Plasma Noradrenaline ◽  
Hypertensive Patients ◽  
Control Subjects

1. The effect of physical exercise on blood pressure, plasma catecholamines and plasma renin activity was studied in fourteen patients with essential hypertension and in eight healthy subjects. 2. Resting plasma noradrenaline and adrenaline and plasma renin activity of the hypertensive patients did not differ from those of the control subjects. 3. In response to graded exercise producing successive heart rates of 120, 140 and 160 beats/min, significantly greater increases of blood pressure were found in the patients than in the control subjects. 4. Plasma noradrenaline increased significantly in both groups at all levels of exercise, the responses being significantly greater in the hypertensive patients. 5. The mean arterial blood pressure was significantly correlated with plasma noradrenaline concentration in the control subjects but not in the hypertensive patients. 6. In the hypertensive group plasma adrenaline increased significantly after exercise at all work loads whereas, in the control group, significant increase occurred only at the highest work load. The differences in the response of the two groups were significant at each work load. 7. Plasma renin activity increased significantly after exercise at the heart rate of 120 beats/min, both in the hypertensive patients and in the control subjects. The magnitude of the response was similar in the two groups.

Elevated Plasma Adrenaline Reflects Sympathetic Overactivity and Enhanced α-Adrenoceptor-Mediated Vasoconstriction in Essential Hypertension

1981 ◽  
Vol 61 (s7) ◽  
pp. 161s-164s ◽  
Author(s):  
P. Bolli ◽  
F. W. Amann ◽  
L. Hulthén ◽  
W. Kiowski ◽  
F. R. Bühler
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Essential Hypertension ◽  
Forearm Blood Flow ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Plasma Adrenaline ◽  
Pressor Test ◽  
Normotensive Subjects

1. Stressful sympathetic stimulation (cold pressor test) was applied to 18 patients with essential hypertension and 15 normotensive subjects. Intra-arterial blood pressure, heart rate, plasma adrenaline and noradrenaline concentrations as well as forearm blood flow were measured before and during the cold pressor test; tests were repeated after regional postsynaptic α1-adrenoceptor blockade with prazosin. 2. Under basal conditions mean blood pressure (P &lt; 0.001), heart rate (P &lt; 0.01), forearm blood flow (P &lt; 0.001) as well as adrenaline concentration (P &lt; 0.01), but not noradrenaline, was higher in patients with essential hypertension. 3. During the cold pressor test, mean blood pressure, heart rate, plasma adrenaline and noradrenaline concentrations increased and forearm flow decreased (all P &lt; 0.001). 4. Stress-stimulated plasma adrenaline was higher in essential hypertensive patients than in normotensive subjects (P &lt; 0.01). In the former the stress-induced increase in plasma adrenaline correlated with the increase in mean blood pressure (r = 0.514; P &lt; 0.05). 5. Prazosin increased forearm blood flow more in essential hypertension (P &lt; 0.001). This increase correlated with the resting plasma adrenaline in the hypertensive (r = 0.710; P &lt; 0.001), but not in normotensive, subjects. 6. When the cold pressor test was repeated during postsynaptic α1-adrenoceptor blockade forearm blood flow did not decrease; instead it increased further in both groups (P &lt; 0.05). 7. Thus in essential hypertension elevated plasma adrenaline concentration reflects sympathetic overactivity as also expressed by enhanced α-adrenoceptor-mediated vasoconstriction.

Renal Haemodynamics and Plasma Renin in Patients with Essential Hypertension

1976 ◽  
Vol 50 (5) ◽  
pp. 409-414 ◽  
Author(s):  
E. B. Pedersen ◽  
H. J. Kornerup
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Vascular Resistance ◽  
Plasma Renin ◽  
Renal Vascular Resistance ◽  
Control Group ◽  
Hypertensive Patients ◽  
Control Subjects ◽  
Hypertensive Group ◽  
Renal Vascular

1. Blood pressure, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in twenty-three patients with essential hypertension and in twenty-one control subjects. Plasma renin concentration was measured in all the hypertensive patients and in fifteen control subjects. 2. GFR and RPF were similar in the hypertensive group and in the control group, whereas the renal vascular resistance was significantly higher in the hypertensive patients. GFR and RPF decreased with increasing blood pressure in both groups. Increasing age induced a further reduction in GFR and RPF in the control subjects but not in the hypertensive patients. 3. Plasma renin concentration in the hypertensive group did not differ from that in the control subjects. The concentration was not correlated to age in either the hypertensive or normal group. 4. Plasma renin index was positively correlated to GFR and RPF and inversely correlated to filtration fraction and renal vascular resistance. 5. It is concluded that GFR and RPF depend on blood pressure in both hypertensive patients and normotensive control subjects. In contrast to the control group, the age effect was negligible in the hypertensive group. It is suggested that renin release depends on changes in renal vascular resistance in the arterioles at the glomerulus and the results support the baroreceptor theory of renin release.

Plasma Noradrenaline Correlates with α-Adrenoreceptor-Mediated Vasoconstriction and Blood Pressure in Patients with Essential Hypertension

1979 ◽  
Vol 57 (s5) ◽  
pp. 177s-180s ◽  
Author(s):  
W. Kiowski ◽  
P. Van Brummelen ◽  
F. R. Bühler
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Essential Hypertension ◽  
Forearm Blood Flow ◽  
Blocking Agent ◽  
Plasma Noradrenaline ◽  
Plasma Noradrenaline Concentration ◽  
Noradrenaline Concentration ◽  
Blood Pressures ◽  
Normotensive Subjects

1. The relationships between plasma noradrenaline concentration at rest and blood pressure, as well as increase in forearm blood flow in response to a brachial artery infusion of the α-adrenoreceptor-blocking agent phentolamine, were investigated in hypertensive and normotensive subjects of similar age. 2. In 44 hypertensive patients plasma noradrenaline correlated with systolic, diastolic and mean blood pressures, but no difference in the mean plasma noradrenaline concentration was found. 3. In 11 patients and 14 normotensive subjects α-adrenoreceptor blockade resulted in a similar increase in forearm blood flow. Only in the patients, however, was this increase related to plasma noradrenaline and blood pressure. 4. In patients with established essential hypertension plasma noradrenaline can be considered to be a marker of α-adrenoreceptor-mediated vasoconstriction, which, in part, determines the height of the blood pressure.

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