ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Vasodilator substances act either directly on vascular smooth muscle (e.g., adenosine) or indirectly (e.g., acetylcholine) on endothelial cells that respond by releasing an unknown powerful, short-lived relaxing factor. To determine whether chronic hypertension or hypercholesterolemia or both would alter the release of the endothelium-derived relaxing factor, experiments were performed in hypertensive rabbits (5-week cellophane wrap perinephritis; mean blood pressure, 134.7 mm Hg) and normotensive rabbits (mean blood pressure, 80 mm Hg) with a Doppler flow transducer and perivascular balloon implanted on the lower abdominal aorta. Rabbits were fed either 1 % cholesterol or control diet for 4 weeks before the experiment. On the day of the experiment, resting hindlimb vascular resistance was greatest in hypertensive rabbits fed 1% cholesterol diet, followed (in descending order) by hypertensive rabbits, normotensive rabbits fed 1% cholesterol diet, and normotensive rabbits. Pharmacological autonomic reflex blockade was induced, and steady state intravenous infusion curves to acetylcholine, serotonin, and adenosine were constructed. Sensitivity (location of effective dose, 50%) to the three vasodilator agents was altered less than twofold from the values in normotensive rabbits for any treatment group. The maximum vasodilator response to acetylcholine, but not to adenosine or serotonin, infusion was reduced significantly in the treated rabbits compared with that in normal rabbits. Reactive hyperemlc responses to 5 to 80 seconds of ischemia were not significantly different among the treatment groups. These results indicate that hypertension with or without hypercholesterolemia does not greatly alter the responsiveness of the hindlimb resistance vasculature to these three vasodilator agents or to ischemia.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The kidneys of adult male spontaneously hypertensive rats (SHR) were denervated, and systemic and regional blood flows were measured 3 to 5 ours or 5 days after denervation. Arterial pressure was reduced 20 to 27% in denervated SHR during both periods compared with that in shamoperated SHR (iliolumbar blood vessles painted with phenol). This hypotnsive response was produced by a 32 to 35% reduction in total peripheral resistance. At 3 to 5 hours and at 5 days, a major decrease in total peripheral resistance was produced by vasodilation in the kidneys and splanchnic organs. Acute urine output, sodium excretion, and plasma renin activity in response to a saline load were not different between sham-operated and denervated SHR. The decreased toal peripheral resistance in denervated SHR may have been secondary to a decreased central sympathetic nerve activity revealed by a decreased maximum response to ganglionic blockade. The results suggest that a pathophysiolgical link may exist between the kidneys and splanchnic organs in genetic hypertension and that specific efferent antiadrenergic or antiafferent nerve therapy, or both, in the kidney may lead to substantial specific decreases not only in renal vascular resistance but also in splanchnic vascular resistance and total peripheral resistance.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effects of exogenous corticotropin releasing factor and arginine vasopressin were evaluated in 6-and 11-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Basal adrenocorticotropic hormone (ACTH) and vasopressin levels did not differ between SHR and WKY, but basal corticosterone level was higher in 6-week-old SHR (p< 0.01). To block endogenous corticotropin releasing factor secretion and nonspecific systemic responses, both groups were pretreated with chlorpromazine, morphine, and sodium pentobarbital anesthesia before measurement of ACTH responses to corticotropin releasing factor and vasopressin infusion. Basal ACTH level was lower in anesthetized 6-week-old SHR than in age-matched WKY (p< 0.01), but no difference was seen between 11-week-old WKY and SHR. The ACTH response to corticotropin releasing factor in 6-week-old WKY was significantly greater than that in age-matched SHR (p< 0.01), whereas in 11-week-old SHR and WKY the response was similar. Compared with responses in WKY, SHR showed an increased ACTH response to high doses of vasopressin (0.25 μg/100 g body weight) at both ages (p< 0.05). These results indicate that the ACTH response to corticotropin releasing factor is blunted in the early stages of hypertension in SHR but later recovers. These abnormal responses to corticotropin releasing factor and vasopressin may be related to the development of spontaneous hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Mean arterial pressure and heart rate were measured during intra-aortic arch (i.a.a.), intravenous, and suprarenal artery (s.r.a.) infusions of adenosine in conscious, unrestrained normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in the absence and presence of ganglionic blockade. In both groups, i.a.a. and i.v. infusions of adenosine induced comparatively larger dose-dependent reductions in mean arterial pressure than did s.r.a. infusions. In WKY, i.a.a. and i.v. infusions of adenosine were equipotent in reducing mean arterial pressure. In contrast, i.a.a. infusion of adenosine was approximately twice as potent as i.v. infusion in SHR. Also, SHR were approximately 6.5 and 2.6 times more sensitive to i.a.a. and i.v. infusions of adenosine, respectively, than were WKY. Further, i.a.a. and s.r.a. infusions of adenosine caused tachycardia in WKY, while i.v. infusions did not alter heart rate. In SHR, neither i.a.a. nor s.r.a. infusion of adenosine altered heart rate, but i.v. infusion induced a profound bradycardia. In ganglionic-blocked WKY that received a norepinephrine infusion to restore blood pressure and heart rate to pre-ganglionic blockade levels, depressor responses to i.a.a. infusion of adenosine were unchanged while the increase in heart rate was abolished. In SHR, ganglionic blockade markedly decreased the depressor response to i.a.a. and i.v. infusions of adenosine and abolished the bradycardic response to i.v. infusion. These results suggest that adenosine is an effective hypotensive agent in both WKY and SHR; however, marked between-strain differences exist in the cardiovascular response to adenosine. These differences most likely are due to changes in adenosine-pulmonary interactions and increases in the importance of adenosine-autonomic interactions in SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Previous studies have suggested that dopamine may have an important role as an inhibitor of aldosterone secretion in humans. Recent studies have also suggested that the adrenergic nervous system may have an important role in controlling aldosterone secretion. The present study investigated the effects of dopamine on aldosterone secretion in response to angiotensin II, with and without pretreatment with propranolol, and to adrenocorticotropic hormone, another known stimulator of aldosterone secretion. Nine normal subjects in balance at 10 mEq sodium intake received dopamine (4 μg/kg/min) or vehicle for 270 minutes on 2 consecutive days on three separate occasions. After 120 minutes of dopamine infusion, the subjects received a 30-minute intravenous infusion of angiotensin II (in cumulative doses of 0.5, 1, 2, 4, and 6 pmol/kg/min), angiotensin II after oral pretreatment with propranolol, or adrenocorticotropic hormone (in cumulative doses of 0.5,1,2, and 5 U/hr). Aldosterone responses to 2,4, and 6 pmol/kg/min of angiotensin II (without propranolol) were greater in vehicle-treated than in dopamine-treated subjects (p< 0.05), as was the slope of the angiotensin H-vehicle dose-response curve (0.46,p< 0.05). Propranolol suppressed the aldosterone response to angiotensin II, but dopamine still inhibited the response. Aldosterone and cortisol secretion were stimulated equally by adrenocorticotropic hormone in dopamine-treated and vehicle-treated groups. These results suggest that dopamine selectively inhibits the aldosterone response to angiotensin II and that this response is not mediated by the activity of dopamine at β-adrenergic receptors.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effects of selective α1-adrenergic blockade with terazosin on blood pressure and cardiovascular pressor responsiveness were assessed in 17 subjects with mild to moderate essential hypertension (mean age, 48 ± 2 [SEM] years). As compared with a 2-week placebo period, 8 weeks of terazosin treatment (mean dose, 10.5 ± 1.7 mg/day) caused a fall of supine (from 153/103 ± 3/2 to 143/96 ± 4/2 mm Hg;p< 0.025) and upright (from 145/106 ± 4/2 to 131/94 ± 5/3 mm Hg;p< 0.01) arterial pressure; a marked blunting of cardiovascular pressor responsiveness to norepinephrine, as judged from the pressor dose (from 73 ± 9 to 2156 ± 496 ng/kg/min;p< 0.02) and from the rightward shift (p< 0.01) of the plasma concentration-blood pressure response curve; and a slight increase in plasma norepinephrine concentration (from 37.7 ± 3.3 to 52.2 ± 7.8 ng/dl;p< 0.01). Heart rate, body weight, exchangeable sodium, blood volume, and norepinephrine plasma clearance; plasma epinephrine, renin, angiotensin II, and aldosterone levels; the relationships between angiotensin H-induced increases in arterial pressure or plasma aldosterone and the concomitant increments of plasma angiotensin II; and heart rate responsiveness to isoproterenol did not change significantly after terazosin treatment. These findings suggest that the fall of arterial pressure induced by selective,-adrenergic blockade in subjects with essential hypertension is associated with, and probably explained by, inhibition of α1-mediated, noradrenergic-dependent vasoconstriction. α1-Adrenergic receptor antagonism did not modify body sodium concentration, the adrenomedullary component of the sympathetic nervous system, angiotensin II levels, or β-adrenergic dependent mechanisms.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effects of captopril on effective renal plasma flow and glomerular filtration rate were studied using a noninvasive radioisotopic method on individual kidneys in eight patients with renovascular hypertension and 12 patients with essential hypertension with various renin levels. Four patients with renovascular hypertension had unilateral while three had bilateral renal artery stenosis. The effective renal plasma flow and glomerular filtration rate were determined by using131I-iodohippurate sodium and “Tc-diethylenetriamine pentaacetic acid, respectively. Glomerular filtration rate and effective renal plasma flow were significantly reduced in the stenotic kidneys of patients with renovascular hypertension compared with values in nonstenotic kidneys (p< 0.01). Treatment with captopril, 37.5 to 75 mg/day for 1 to 48 weeks, further reduced the glomerular filtration rate only in stenotic kidneys, and effective renal plasma flow increased in both kidney types. In two of the three renal hypertensive patients with bilateral renal artery stenosis, captopril produced a reversible azotemia that was unrelated to the fall in blood pressure, as evidenced by the lack of azotemia seen after a moderate blood pressure reduction induced by other antihypertensive medications. These results indicate that endogenous angiotensin II is essential in maintaining the glomerular filtration rate in stenotic kidneys and suggest that a reduction in glomerular filtration rate during captopril administration could indicate the presence of renal artery stenosis.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Essential hypertension is thought to produce a uniform exaggerated natriuresis and diuresis. Because validation of this formulation in humans is incomplete, the natriuretic and diuretic responses to acute volume expansion were characterized by using water immersion to the neck. This method provides a volume stimulus identical to that induced by 2 L of saline without plasma compositional change. Twenty-seven subjects with essential hypertension were studied on three occasions in the seated posture while in balance on a 10 mEq Na, 100 mEq K diet: during the seated control study, during 4 hours of head-out immersion, and during saline infusion (2 L/2 hours). Four subjects had exaggerated urinary Na excretion in response to neck immersion (Group 3), and 16 had a normal response (Group 2) indistinguishable from that of 15 previously studied normal subjects. The remaining seven subjects (Group 1) had blunted or absent natriuretic responses compared with that in normal subjects (p< 0.005). Similar results were obtained with saline administration; cumulative Na excretion in Group 1 was markedly less than that in Group 2 and the normal subjects. The heterogeneity in Na excretion indicates that an exaggerated natriuresis is not a uniform concomitant of essential hypertension. The significant inverse correlation between basal plasma aldosterone level and peak urinary as well as cumulative Na excretion suggests that plasma aldosterone constitutes a determinant of the differing natriuretic responses. In contrast to findings with urinary Na excretion, the diuretic responses of Groups 1 and 2 were identical. The striking dissociation between renal Na and water handling underscores the specificity of the derangement in renal Na handling.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID