Retinal arteriolar responses to acute severe elevation in systemic blood pressure in cats: Role of endothelium-derived factors

Abstract Background Epidemiology of pulmonary arterial hypertension (PAH) is changing and the age at diagnosis and the prevalence of comorbidities are increasing but their prognostic relevance is substantially undefined. Purpose To evaluate the prognostic value of comorbidities in patients with PAH and in the different clinical subgroups. Methods All patients with PAH referred to a single centre underwent baseline right heart catheterization, brain natriuretic peptide (BNP) plasma levels, 6-min walking distance (6MWD), WHO functional class and anamnestic comorbidities evaluation. Cox regression model was used for analysis (p-value <0.1 was considered for inclusion in multivariate analysis). Results 1311 patients were included [age 51 years; aetiology: 522 idiopathic/heritable/drug-induced (I/H/D)-PAH, 258 connective tissue disease (CTD)-associated PAH, 242 congenital heart disease (CHD)-associated PAH, 196 portal hypertension/HIV (PoHIV)-associated PAH and 93 pulmonary veno-occlusive disease (PVOD)]. 5% of patients have no comorbidities. At multivariate analysis comorbidities independently associated with prognosis are: systemic hypertension in I/H/D [HR 0.616, p=0.030], mean systemic blood pressure in CTD [HR 0.980, p=0.002] and PVOD [HR 0.962, p=0.006], dyslipidemia in CTD [HR 0.447, p=0.001] and PoHIV [HR 0.201, p=0.026], estimated glomerular filtration rate in PoHIV [HR 1.000, p<0.001] and body mass index (BMI) [HR 0.966, p=0.069] in CTD. In CHD comorbidities are not independent determinants of prognosis. Other variables independently predictive of a worse prognosis are: advanced age in all PAH subgroups except PVOD; male gender in I/H/D; reduced 6MWD in I/H/D, CTD and PVOD; high BNP in I/H/D, CHD and PVOD; low cardiac index in CTD, high right atrial pressure in I/H/D and low mixed venous oxygen saturation in CHD. Conclusion The age at PAH diagnosis and the prevalence of comorbidities are increasing but their prognostic role seems of poor relevance as we found a protective role of these variables: high systemic blood pressure (maybe indicative of a better haemodynamic stability) in I/H/D, CTD and PVOD; dyslipidemia and high BMI (maybe indicative of a better nutritional status and a less severe autoimmune disease) in CTD; dyslipidemia and a high glomerular filtration rate (both indicative of a less severe liver disease) in PoHIV. Funding Acknowledgement Type of funding source: None

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Effects of artificial bleeding upon the systemic blood pressure and the blood flow of the internal carotid artery and the role of the sinus nerve in rabbits

Journal of Nippon Medical School ◽

10.1272/jnms1923.45.181 ◽

1978 ◽

Vol 45 (3) ◽

pp. 181-186

Author(s):

Masanori Ikeda

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Carotid Artery ◽

Internal Carotid Artery ◽

Internal Carotid ◽

Systemic Blood Pressure ◽

Systemic Blood

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Role of paraventricular nucleus in control of blood pressure and drinking in rats

AJP Renal Physiology ◽

10.1152/ajprenal.1992.262.6.f1068 ◽

1992 ◽

Vol 262 (6) ◽

pp. F1068-F1075 ◽

Cited By ~ 4

Author(s):

L. L. Jensen ◽

J. W. Harding ◽

J. W. Wright

Keyword(s):

Blood Pressure ◽

Paraventricular Nucleus ◽

Critical Role ◽

Systemic Blood Pressure ◽

Dependent Manner ◽

Ang Ii ◽

Sprague Dawley ◽

Systemic Blood ◽

Dose Dependent

The present investigation examined the abilities of angiotensin (ANG) II and III to produce increases in blood pressure and drinking when microinfused into the paraventricular nucleus (PVN) of the hypothalamus of the Sprague-Dawley rat. Dose-dependent elevations in systemic blood pressure and heart rate were measured to both ANG II and III in the anesthetized rat, with ANG II more potent than ANG III at the two highest doses examined. Pretreatment with the specific ANG receptor antagonist [Sar1,Thr8]ANG II (sarthran), blocked subsequent ANG II- and III-induced elevations in blood pressure, suggesting that these responses were dependent on the activation of ANG receptors. A similar analysis in awake rats yielded nearly equivalent results. A final experiment demonstrated that microinfusions of ANG II and III into the PVN produced drinking in a dose-dependent manner, with greater consumption to ANG II than ANG III. Again, sarthran was found to block the dipsogenic response. Histological examination revealed that the location of the injection site was linked to the character of the ANG-dependent response. These data suggest that the PVN may play a critical role in mediating central ANG effects on body water homeostasis and blood pressure regulation. Furthermore, it appears that subnuclei of the PVN may participate differentially in ANG-mediated actions.

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The role of thromboxane in two-kidney, one-clip Goldblatt hypertension in rats

AJP Renal Physiology ◽

10.1152/ajprenal.1989.257.2.f190 ◽

1989 ◽

Vol 257 (2) ◽

pp. F190-F196 ◽

Cited By ~ 4

Author(s):

S. I. Himmelstein ◽

P. E. Klotman

Keyword(s):

Blood Pressure ◽

Receptor Antagonist ◽

Volume Regulation ◽

Systemic Blood Pressure ◽

Arachidonic Acid Metabolism ◽

Systemic Hypertension ◽

Systemic Blood ◽

Contralateral Kidney ◽

Synthase Inhibitor

Impaired contralateral kidney (CLK) function is important in the maintenance of hypertension in the two-kidney, one-clip (2K, 1C) Goldblatt rat model. Since glomerular filtration rate (GFR) is influenced by the products of arachidonic acid metabolism, we investigated the potential role of eicosanoids as mediators of impaired CLK pressure-volume regulation. At 4 wk following right renal artery clipping, GFR of hypertensive rats was significantly reduced. This decrease was due to the fixed reduction in GFR of the clipped kidney and failure of the CLK to increase its GFR. Thromboxane (Tx) production by isolated perfused CLK was significantly elevated, whereas prostacyclin production remained unchanged. Furthermore, CLK GFR was inversely proportional to Tx production. Treatment of 4-wk hypertensive animals with either the Tx synthase inhibitor UK-38,485 or the Tx receptor antagonist GR 32191 produced a significant increase in CLK GFR. In addition, treatment with either the Tx synthase inhibitor or the Tx receptor antagonist significantly reduced systemic blood pressure. Thus, in this 2K, 1C model of hypertension, increased renal Tx production prevents functional hypertrophy of the contralateral kidney. As a result, CLK pressure-volume regulation is impaired and systemic hypertension is maintained. Furthermore, Tx antagonists restore CLK function and acutely lower systemic blood pressure. Therefore, increased renal Tx production by the CLK appears to be an important mediator of hypertension in the 2K, 1C model.

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Collecting duct-specific knockout of the endothelin A receptor alters renal vasopressin responsiveness, but not sodium excretion or blood pressure

AJP Renal Physiology ◽

10.1152/ajprenal.00100.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. F692-F698 ◽

Cited By ~ 75

Author(s):

Yuqiang Ge ◽

Peter K. Stricklett ◽

Alisa K. Hughes ◽

Masashi Yanagisawa ◽

Donald E. Kohan

Keyword(s):

Blood Pressure ◽

Collecting Duct ◽

Receptor Gene ◽

Plasma Osmolality ◽

Systemic Blood Pressure ◽

Systemic Blood ◽

Endothelin A Receptor ◽

Nephron Segment ◽

Normal Water

Collecting duct (CD)-specific knockout (KO) of endothelin-1 (ET-1) causes hypertension, impaired ability to excrete a Na load, and enhanced CD sensitivity to the hydrosmotic effects of vasopressin (AVP). CD express the two known ET receptors, ETA and ETB; in the current study, the role of the CD ETA receptor in mediating ET-1 actions on this nephron segment was evaluated. The ETA receptor gene was selectively disrupted in CD (CD ETA KO). CD ETA KO mice had no differences in systemic blood pressure, Na or K excretion, and plasma aldosterone or renin activity in response to a normal- or a high-Na diet compared with controls. During normal water intake, urinary osmolality (Uosm), plasma Na concentration, and plasma osmolality were not affected, but plasma AVP concentration was increased in CD ETA KO animals (0.57 ± 0.25 pg/ml in controls and 1.30 ± 0.29 pg/ml in CD ETA KO mice). CD ETA KO mice had a modestly enhanced ability to excrete an acute, but not a chronic, water load. DDAVP infusion increased Uosm similarly; however, CD ETA KO mice had a more rapid subsequent fall in Uosm during sustained DDAVP administration. CD suspensions from CD ETA KO mice had a 30–40% reduction in AVP- and forskolin-stimulated cAMP accumulation. These data indicate that CD ETA KO decreases renal sensitivity to the urinary concentrating effects of AVP and suggest that activation of the ETA receptor downregulates ET-1 inhibition of AVP actions in the CD. Furthermore, the CD ETA receptor does not appear to be involved in modulation of systemic blood pressure or renal Na excretion under physiological conditions.

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Sympathetically mediated increases in cardiac output, not restraint of peripheral vasodilation, contribute to blood pressure maintenance during hyperinsulinemia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00250.2020 ◽

2020 ◽

Vol 319 (1) ◽

pp. H162-H170 ◽

Cited By ~ 2

Author(s):

Jacqueline K. Limberg ◽

James A. Smith ◽

Rogerio N. Soares ◽

Jennifer L. Harper ◽

Keeley N. Houghton ◽

...

Keyword(s):

Blood Pressure ◽

Cardiac Output ◽

Systemic Blood Pressure ◽

Experimental Protocol ◽

Systemic Blood ◽

Peripheral Vasodilation ◽

Experimental Protocols ◽

Isolated Arteries ◽

Principal Contributor

We examined the role of sympathetic activation in restraining vasodilatory responses to hyperinsulinemia and sustaining blood pressure in healthy adults. Data are reported from two separate experimental protocols in humans and one experimental protocol in isolated arteries from mice. Contrary to our hypothesis, the present findings support the idea that during hyperinsulinemia, a sympathetically mediated increase in cardiac output, rather than restraint of peripheral vasodilation, is the principal contributor to the maintenance of systemic blood pressure.

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