angiotensin-iii and Hypertension--Renovascular

Topics: Angiotensin I; Angiotensin II; Angiotensin III; Biomarkers; Chromatography, High Pressure Liquid; Cushing Syndrome; Diagnosis, Differential; Diagnostic Techniques, Endocrine; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renovascular; Myocardial Infarction; Radioimmunoassay; Reference Values; Renin-Angiotensin System; Specimen Handling; Water-Electrolyte Imbalance

Topics: Adrenal Cortex; Adrenal Cortex Function Tests; Aldosterone; Angiotensin II; Angiotensin III; Humans; Hypertension, Malignant; Hypertension, Renovascular

There is an increased number of in vitro evidence that angiotensin II (Ang II) may promote thrombosis. However there are no in vivo experiments exploring the effect of Ang II on thrombus formation. In the present study we have investigated the influence of Ang II on venous thrombosis in renovascular hypertensive rats. Furthermore, we examined the role of AT(1) receptor and Ang II metabolites: angiotensin III (Ang III) and angiotensin IV (Ang IV) in the mechanisms of Ang II action. The contribution of coagulation and fibrinolytic systems in the mode of Ang II action was also determined. Venous thrombosis was induced by ligation of vena cava. Ang II infused into rats developing venous thrombosis caused dose-dependent increase in thrombus weight, which was partially reversed by losartan, selective AT(1) antagonist. Ang III did not influence the thrombus formation in hypertensive rats, while Ang IV caused a marked increase in thrombus weight only in one of the used doses. Our study shows that Ang II via AT(1) receptor enhances thrombosis development. The prothrombotic effect of Ang II may partially depend on enhanced leukocytes adhesion to endothelial cells accompanied by accelerated fibrin formation and increased plasma level of PAI-1. Moreover, Ang II action is partially mediated by one of its metabolites - Ang IV.

Topics: alpha-2-Antiplasmin; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin III; Animals; Blood Pressure; Carotid Arteries; Fibrin; Heart Rate; Hypertension, Renovascular; Infusions, Intravenous; Losartan; Male; Plasminogen Activator Inhibitor 1; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Recombinant Proteins; Regional Blood Flow; Tissue Plasminogen Activator; Venous Thrombosis

1. The antihypertensive and renal effects of cilazapril, a new angiotensin converting enzyme inhibitor, were evaluated in both two-kidney, one-clip Goldblatt hypertensive rats (n = 11) and normotensive rats (n = 6). 2. Intravenous infusion of cilazapril (1 mg/kg followed by 25 micrograms min-1 kg-1) caused significant reductions of blood pressure from 163 +/- 3 to 122 +/- 4 mmHg and from 157 +/- 2 to 113 +/- 3 mmHg in two separate groups of hypertensive rats and from 124 +/- 1 to 105 +/- 2 mmHg in normotensive rats. The hypotensive effect in terms of absolute value of percentage change was greater in hypertensive rats than in normotensive rats (41 +/- 6 vs 20 +/- 3 mmHg or 25 +/- 4% vs 16 +/- 2%, respectively). 3. Cilazapril increased glomerular filtration rate, urine flow, and absolute and fractional excretion rates of sodium and potassium in the non-clipped kidney of hypertensive rats. In contrast, the clipped kidney exhibited a depressed renal function during cilazapril infusion. 4. In normotensive rats, the hypotensive and enhanced renal function responses to cilazapril were much less than those of the non-clipped kidney of hypertensive rats. 5. Superimposed administration of either angiotensin II or angiotensin III during cilazapril infusion completely reversed the blood pressure and bilateral renal responses of cilazapril in both hypertensive and normotensive rats. 6. These results indicate that cilazapril reduces arterial pressure and enhances renal excretion mainly via inhibition of angiotensin II and angiotensin III formation.

Topics: Angiotensin II; Angiotensin III; Angiotensins; Animals; Blood Pressure; Cilazapril; Diuresis; Glomerular Filtration Rate; Hypertension, Renovascular; Kidney; Male; Natriuresis; Pyridazines; Rats; Rats, Inbred Strains

In the present study, effects of angiotensin on the adrenal steroidogenesis were studied in essential hypertension, primary aldosteronism and renovascular hypertension (RVH). Angiotensin III(A III), an analogue of angiotensin II, was administered to 17 normal volunteers (9 male and 8 female), 44 patients with essential hypertension (EH) (15 with high renin; HREH, 15 with normal renin; NREH and 14 with low renin; LREH), 8 patients with primary aldosteronism (5 with adrenal adenoma; APA and 3 with bilateral adrenocortical hyperplasia; IHA) and 5 patients with renovascular hypertension. In all the patients with hypertension and normal subjects, blood pressure (BP) and plasma concentrations of progesterone (P), corticosterone (B), aldosterone (Aldo), 17 alpha-hydroxyprogesterone(17-OHP) and cortisol(F) were measured before and after intravenous administration of A III (0.1, 0.5, 1.0, 10, 20 and 40 ng/kg/min, for 15 min, respectively). 1) BP rose from 164 +/- 19/88 +/- 8 to 180 +/- 19/112 +/- 10 mmHg [systolic BP(SBP); P less than 0.01, diastolic BP(DBP); P less than 0.01] in HREH, from 162 +/- 12/96 +/- 7 to 186 +/- 11/118 +/- 8 mmHg in NREH(SBP; P less than 0.01, DBP; P less than 0.01), 165 +/- 12/94 +/- 8 to 202 +/- 12/126 +/- 9 mmHg in LREH(SBP; P less than 0.001, P less than 0.001) and 118 +/- 8/72 +/- 7 mmHg to 136 +/- 11/88 +/- 8 mmHg in controls (SBP; P less than 0.01, DBP; P less than 0.01). The elevation in NREH and LREH was greater than that in HREH and controls. The elevations of BP both in APA and IHA were remarkably greater than that in controls and as similar as LREH(APA; 174 +/- 21/103 +/- 12 to 204 +/- 18/136 +/- 8 mmHg, IHA; 176 +/- 10/104 +/- 4 to 206 +/- 17/138 +/- 10 mmHg). The elevation in RVH was similar to that in NREH(173 +/- 9/108 +/- 8 to 194 +/- 13/132 +/- 10 mmHg). 2) Plasma P increased from 25.5 +/- 7.5 to 39.5 +/- 13.8 ng/100 ml(P less than 0.001) in HREH, from 28.0 +/- 7.7 to 45.3 +/- 12.7 ng/100 ml(P less than 0.001) in NREH, from 23.8 +/- 8.2 to 47.2 +/- 19.4 ng/100 ml(P less than 0.001) in LREH and 26.6 +/- 11.0 to 43.4 +/- 14.6 ng/100 ml in controls. The increment in HREH or NREH was similar to that in controls(P less than 0.1, respectively), whereas greater than controls in LREH(P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Adult; Aldosterone; Angiotensin II; Angiotensin III; Circadian Rhythm; Corticosterone; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Hyperaldosteronism; Hypertension; Hypertension, Renovascular; Infusions, Intravenous; Male; Middle Aged; Progesterone

Sixteen dogs were instrumented for recording mean arterial blood pressure (MAP) and blood flow from the left renal artery (RBF) and for intra-arterial infusions of norepinephrine (NE) and angiotensin II (ANG II). Nine dogs (group 1) were studied while normotensive and also when hypertensive. Seven control dogs (group 2) were studied only when normotensive. In a control session conducted in group 1 and at weekly intervals for up to 6-12 wk after the right renal artery was clipped, infusions of NE and ANG II were given intra-arterially to produce graded decreases in RBF. Group 2 was studied similarly in a control session and 4-7 wk later. Regressions of the values of percent change RBF (arc sin transformation) on the concentrations of NE and ANG II in renal arterial blood estimated the renal vascular reactivity of the hypertensives' contralateral kidney and the normotensives' kidney. In group 1, during the postclipping intervals when MAP and plasma renin activity were increased, the renal vascular reactivity to NE, but not to ANG II was increased. This was based on the significant elevation above the X axis in the postclipping regressions. In group 2, MAP, plasma renin activity, and renal vascular reactivity to NE and ANG II were unchanged over the 4- to 7-wk interval of study. These results indicate that the contralateral kidney develops an increased vascular reactivity to NE but not to ANG II in Goldblatt hypertension.

Topics: Angiotensin III; Animals; Blood Pressure; Dogs; Female; Hypertension, Renovascular; Injections, Intra-Arterial; Male; Norepinephrine; Renal Artery; Renal Circulation; Renin; Vascular Resistance; Vasomotor System; Wakefulness