Abstract MP40: Hiv Impairs Endothelial Function And Elevates Blood Pressure Via Tnfa Dependent Mechanisms In Male And Female Mice.

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Taylor Kress ◽  
Eric J Belin De Chantemele ◽  
Jessica L Faulkner ◽  
Thiago Bruder do Nascimento

HIV is a major health concern with over 37 million individuals worldwide living with HIV. The onset of combination antiretroviral therapy (cART) patients with HIV (PWH) live longer but exhibit accelerated development of cardiovascular disease. Clinical evidence indicates that 35% of PWH exhibit hypertension, however, the etiopathology is still ill-defined. We plan to take advantage of a transgenic mouse model (Tg26) that mimics patients with a repressed virus, to test the hypothesis that viral infection independent of cART induces endothelial dysfunction and hypertension via a TNF-α mediated mechanism. Vascular reactivity was analyzed via wire myography and blood pressure (BP) recorded via radio-telemetry. Results showed that viral infection impaired aorta endothelium-dependent relaxation as reflected by a decrease in acetylcholine-mediated relaxation in both Tg26 mice (P<0.05) which was ameliorated with the NOX 1/4 inhibitor GKT 137831. Smooth muscle cell-dependent relaxation (SNP) and contractility to phenylephrine and KCl remained intact in Tg26 mice. Viral infection increased systolic, diastolic, and mean arterial pressure (MAP: male: WT=112.3±1.3 vs Tg26=121.9±4.0 mmHg/ female: WT=110.6±3.01/ Tg26=120.3±6.9 mmHg) and elevated heart rate (HR) in both sexes (p<0.05). We used atropine, propranolol, and hexamethonium in WT and Tg26 mice to investigate the contribution of the autonomic nervous system to hypertension. HR responses to both atropine (Female: +5.07±2.8% vs. male +4.3±5.4% of baseline) and propranolol (Female: 19.9±6.1% vs. male 12.0±4.3%) revealed no significance or sex differences in WT mice and no effects of viral infection on autonomic control of heart rate in Tg26 mice. BP responses to hexamethonium revealed no effect of sex or viral infection, supporting a limited contribution of the autonomic nervous system to hypertension in Tg26 mice. However, we found that TNFα inhibition with etanercept reduced mean arterial pressure in Tg26 mice to the level of the WT mice (WT=112.3±1.3, Treated=110.1±0.185) and improved endothelial function. These data indicate that HIV infection contributes to cardiovascular disease via inducing endothelial dysfunction and hypertension via NOX and TNFα-dependent mechanisms respectively.

1995 ◽  
Vol 268 (6) ◽  
pp. H2302-H2310 ◽  
Author(s):  
G. Weichert ◽  
C. A. Courneya

We examined the response to hemorrhage in conscious normotensive and hypertensive rabbits under control conditions and during efferent blockade of 1) the hormones vasopressin (AVP) and angiotensin II (ANG II), 2) the autonomic nervous system, and 3) autonomic and hormonal inputs. We recorded mean arterial pressure, heart rate, and hindlimb conductance. The response to hemorrhage was unchanged with hormonal blockade alone. Blockade of the autonomic nervous system caused a faster rate of blood pressure decline, but the rate of decrease in hindlimb conductance was maintained at control levels. Blocking the autonomic nervous system and the hormones resulted in rapid blood pressure decline and an increase in hindlimb conductance. Although the three types of efferent blockade had a similar pattern of effects in normotensive and hypertensive rabbits, hypertensive rabbits exhibited less cardiovascular support during hemorrhage than normotensive rabbits. During hemorrhage, hypertensive rabbits had an attenuation of hindlimb vasoconstriction, a reduction in the heart rate-mean arterial pressure relationship, and reduced ability to maintain blood pressure compared with normotensive rabbits.


1995 ◽  
Vol 269 (5) ◽  
pp. H1570-H1577
Author(s):  
C. A. Courneya ◽  
G. Weichert

Hypertensive (HT) rabbits have impaired reflex control of heart rate and vascular tone, which is, at least in part, related to dysfunctional baroreceptors. We hypothesized that reflex control of vasopressin (AVP) would also be impaired in the HT rabbit. To test this, we compared hemorrhage-induced increases in AVP between conscious normotensive (NT) and HT rabbits. The hemorrhage-induced rise in AVP was found to be significantly (P < 0.05) attenuated in the HT rabbits. We tested a second hypothesis, that the observed impairment was related to arterial baroreceptor function, by hemorrhaging the same rabbits after reversible cardiac denervation. Under these conditions, only the arterial baroreceptors would be expected to contribute to reflex control of AVP. Impairment was still evident after cardiac denervation; that is, the hemorrhage-induced rise in AVP was significantly (P < 0.01) attenuated in the cardiac-denervated HT rabbits compared with NT rabbits. Thus impairment was, at least in part, related to arterial baroreceptors. Previously, we showed in NT rabbits that AVP only contributed to maintenance of arterial pressure (during hemorrhage), after the autonomic nervous system (ANS) had been blocked. Thus, in the present study, we compared the maintenance of arterial pressure during hemorrhage between NT and HT rabbits after ANS blockade. Blood pressure maintenance was significantly attenuated in the HT rabbits (P < 0.05). In addition, for a given fall in pressure, significantly less AVP (P < 0.05) was released in the ANS-blocked HT rabbits as compared with NT rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)


1999 ◽  
Vol 277 (5) ◽  
pp. H1872-H1877 ◽  
Author(s):  
John B. Buckwalter ◽  
Philip S. Clifford

The purpose of this study was to determine whether the autonomic nervous system is involved in skeletal muscle vasodilation at the onset of exercise. Mongrel dogs ( n = 7) were instrumented with flow probes on both external iliac arteries. Before treadmill exercise at 3 miles/h, 0% grade, hexamethonium (10 mg/kg) and atropine (0.2 mg/kg) or saline was infused intravenously. Ganglionic blockade increased resting heart rate from 87 ± 5 to 145 ± 8 beats/min ( P < 0.01) and reduced mean arterial pressure from 100 ± 4 to 88 ± 5 mmHg ( P < 0.01). During steady-state exercise, heart rate was unaffected by ganglionic blockade (from 145 ± 8 to 152 ± 5 beats/min), whereas mean arterial pressure was reduced (from 115 ± 4 to 72 ± 4 mmHg; P < 0.01). Immediate and rapid increases in iliac blood flow and conductance occurred with initiation of exercise with or without ganglionic blockade. Statistical analyses of hindlimb conductance at 5-s intervals over the first 30 s of exercise revealed a statistically significant difference between the control and ganglionic blockade conditions at 20, 25, and 30 s ( P < 0.01) but not at 5, 10, and 15 s of exercise. Hindlimb conductance at 1 min of exercise was 9.21 ± 0.68 and 11.82 ± 1.32 ml ⋅ min−1 ⋅ mmHg−1for the control and ganglionic blockade conditions, respectively. Because ganglionic blockade did not affect the initial rise in iliac conductance, we concluded that the autonomic nervous system is not essential for the rapid vasodilation in active skeletal muscle at the onset of exercise in dogs. Autonomic control of skeletal muscle blood flow during exercise is manifested through vasoconstriction and not vasodilation.


2003 ◽  
Vol 81 (11) ◽  
pp. 1036-1041 ◽  
Author(s):  
Sanya Roysommuti ◽  
Mahmood S Mozaffari ◽  
J Michael Wyss

Insulin excess exacerbates hypertension in spontaneously hypertensive rats (SHR). This study examined the relative contribution of the renin–angiotensin system and the sympathetic nervous system in this phenomenon. In SHR, daily subcutaneous injections of insulin were initiated either before short-term angiotensin-converting enzyme inhibition with captopril or after lifetime captopril treatment. Insulin treatment resulted in significant increases in mean arterial pressure and heart rate and captopril treatment lowered arterial pressure, but captopril did not lower arterial pressure more in the insulin-treated compared with control rats. To test the contribution of the sympathetic nervous system to this form of hypertension, each rat was intravenously infused with either a ganglionic blocker (i.e., hexamethonium) or a centrally acting α2-adrenergic receptor agonist (i.e., clonidine). Administration of either agent largely eliminated the differences in mean arterial pressure and heart rate between the insulin-treated and saline-treated SHR, irrespective of captopril treatment. These data indicate that in SHR, the ability of insulin to increase blood pressure is closely related to sympathoexcitation, which is unresponsive to blockade of angiotensin-converting enzyme.Key words: blood pressure, insulin, captorpil, hexamethonium, clonidine, rat.


1998 ◽  
Vol 95 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Gianfranco PICCIRILLO ◽  
Santagada ELVIRA ◽  
Emanuela VIOLA ◽  
Carmela BUCCA ◽  
Michele DURANTE ◽  
...  

1.The influence of anxiety symptoms on autonomic nervous system cardiovascular control has never been studied in hypertensive subjects. This study was designed to verify the presence of sympathetic hyperactivity in hypertension associated with anxiety symptoms. 2.Neuroautonomic cardiovascular control was evaluated using short-time power spectral analysis of RR and arterial pressure variability at baseline and after the head-up tilt test. The two spectral components principally influenced by the autonomic nervous system are the low-frequency (LF) component, mainly though not exclusively due to sympathetic modulation, and the high-frequency (HF) component, due to parasympathetic activity. The ratio of LF to HF powers (LF:HF) provides an index of the sympathovagal sinus balance. 3.We studied 33 hypertensive subjects (mean age 47±1 years; M:F = 19:14) and 37 normotensive control subjects (mean age: 47±2 years; M:F = 20:17) divided into four subgroups: hypertensive subjects who scored 2 or more on a 5-item anxiety symptom scale, hypertensive subjects who scored 0, normotensive controls who scored 2 or more and normotensive controls who scored 0. LF:HF and LF during rest were significantly higher (P< 0.05) in hypertensive and normotensive groups with an anxiety score of 2 or more compared with the two groups who scored 0. HF of systolic blood pressure was significantly lower in the hypertensive group who scored 2 or more than in the hypertensive group who scored 0 (P< 0.05). Tilt in both hypertensive groups reporting anxiety symptoms left the indexes of sympathetic modulation unchanged. Tilt in hypertensive subjects reporting anxiety symptoms also induced a significant fall in arterial pressure (P< 0.05). The mean left ventricular mass index was significantly higher in the hypertensive subjects who had anxiety scores of 2 or more than in those scoring 0 (144.7±3.0 versus 133.4±2.31, P< 0.05). 4.In conclusion, normotensive and hypertensive subjects reporting anxiety symptoms showed increased sympathetic modulation of heart rate at rest. Higher anxiety scores seem to be associated with the development of left ventricular hypertrophy.


1998 ◽  
Vol 94 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Sharmini Puvi-Rajasingham ◽  
Gareth D. P. Smith ◽  
Adeola Akinola ◽  
Christopher J. Mathias

1. In human sympathetic denervation due to primary autonomic failure, food and exercise in combination may produce a cumulative blood pressure lowering effect due to simultaneous splanchnic and skeletal muscle dilatation unopposed by corrective cardiovascular reflexes. We studied 12 patients with autonomic failure during and after 9 min of supine exercise, when fasted and after a liquid meal. Standing blood pressure was also measured before and after exercise. 2. When fasted, blood pressure fell during exercise from 162 ± 7/92 ± 4 to 129 ± 9/70 ± 5 mmHg (mean arterial pressure by 22 ± 5%), P < 0.0005. After the meal, blood pressure fell from 159 ± 8/88 ± 6 to 129 ± 6/70 ± 4 mmHg (mean arterial pressure by 22 ± 3%), P < 0.0001, and further during exercise to 123 ± 6/61 ± 3 mmHg (mean arterial pressure by 9 ± 3%), P < 0.01. The stroke distance—heart rate product, an index of cardiac output, did not change after the meal. During exercise, changes in the stroke distance—heart rate product were greater when fasted. 3. Resting forearm and calf vascular resistance were higher when fasted. Calf vascular resistance fell further after exercise when fasted. Resting superior mesenteric artery vascular resistance was lower when fed; 0.19 ± 0.02 compared with 032 ± 0.06, P < 0.05. After exercise, superior mesenteric artery vascular resistance had risen by 82%, to 0.53 ± 0.12, P < 0.05 (fasted) and by 47%, to 0.29 ± 0.05, P < 0.05 (fed). 4. On standing, absolute levels of blood pressure were higher when fasted [83 ± 7/52 ± 7 compared with 71 ± 2/41 ± 3 (fed), each P < 0.05]. Subjects were more symptomatic on standing post-exercise when fed. 5. In human sympathetic denervation, exercise in the fed state lowered blood pressure further than when fasted and worsened symptoms of postural hypotension.


Author(s):  
Sidharth Sraban Routray ◽  
Ramakanta Mohanty

ABSTRACTObjective: During laparoscopic surgeries, pneumoperitoneum can lead to various pathophysiologic changes in the cardiovascular system resulting inhypertension and tachycardia. Search for ideal drug to prevent this hemodynamic response goes on. The aim of our study was to evaluate the effect oforally administered moxonidine in attenuating the hemodynamic responses that occur during the laparoscopic surgeries.Methods: A total of 50 adult acetylsalicylic acid I and II patients scheduled for elective laparoscopic surgeries were selected for this prospectiverandomized double-blinded study. They were randomly allocated into two groups: moxonidine group (M) and placebo group (P). M group receivedoral moxonidine 0.3 mg at 8 pm on the day before surgery and at 8 am on the day of surgery. P group received a placebo at the same timing as that ofthe M group.Results: Following pneumoperitoneum rise in systolic blood pressure (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and heart rate (HR)was higher in P group in comparison to M group which was statistically significant.Conclusion: Significant rise in HR, SBP, DBP, and mean BP was noted in the P group in comparison to moxonidine group. Moxonidine provided betterperioperative hemodynamic stability in patients undergoing laparoscopic surgeries.Keywords: Moxonidine, Stress response, Laparoscopic.


2020 ◽  
Vol 9 (1) ◽  
pp. 8-15
Author(s):  
Arya Justisia Sani ◽  
Ardhana Tri Arianto ◽  
Muhammad Husni Thamrin

Latar Belakang dan Tujuan: Peningkatan respon hemodinamik yang disebabkan oleh nyeri dapat menyebabkan peningkatan aliran darah otak dan tekanan intrakranial. Blok scalp pada kraniotomi menumpulkan respon hemodinamik karena rangsangan nyeri serta mengurangi penambahan analgesi lain. Penelitian ini bertujuan untuk mengetahui efektifitas blok scalp sebagai analgetik pada kraniotomi.Subjek dan Metode: Penelitian ini menggunakan uji klinik acak tersamar ganda pada 36 pasien dengan status fisik ASA 1–3 dilakukan operasi kraniotomi eksisi dan memenuhi kriteria inklusi. Sampel dibagi menjadi kelompok I (dengan blok scalp) dan kelompok II (tanpa blok scalp). Blok dilakukan sesaat setelah induksi anestesi. Digunakan levobupivakain 0,375% sebanyak 3 ml tiap insersi, pada masing-masing saraf. Tekanan darah, tekanan arteri rata-rata, detak jantung sebelum intubasi dan setelah intubasi, pemasangan pin, insisi kulit dan insisi duramater serta total kebutuhan fentanyl tambahan dicatat. Data yang diperoleh dianalisis dengan program komputer SPSS versi 17 lalu diuji menggunakan uji Kruskal-Wallis atau One-way ANOVA. Batas kemaknaan yang diambil adalah p < 0,05.Hasil: Selama kraniotomi, detak jantung, tekanan darah, tekanan arteri rata-rata secara signifikan lebih tinggi pada pasien tanpa blok scalp terutama pada saat pemasangan pin. Hasil uji statistik menunjukkan perbedaan signifikan, penambahan fentanyl pada pasien dengan blok scalp lebih sedikit dibandingkan tanpa blok scalp, p=0,000 (p<0,05).Simpulan: Blok scalp levobupivakain efektif dalam menurunkan respon hemodinamik terutama pada saat pemasangan pin. Pasien kraniotomi dengan blok scalp membutuhkan penambahan fentanyl lebih sedikit. Differences on Hemodynamic Response with Levobupivacaine Scalp Block in Craniotomy SurgeryAbstractBackground and Objective: Increased hemodynamic response caused by pain can lead to increased cerebral blood flow and intracranial pressure. Scalp block in craniotomy blunts hemodynamic response due to pain and reduce other analgesics addition. This study aims to determine effectiveness of scalp blocks as analgesic in craniotomy.Subject and Method: This study used a double-blind randomized clinical trial in 36 patients with physical status ASA 1-3 who underwent craniotomy and met inclusion criteria. Samples were divided into group I (with scalp block) and group II (without scalp block). Scalp Block was performed right after anesthesia induction. Using levobupivacaine 0.375% 3 ml for each insertion. Blood pressure, mean arterial pressure, heart rate before and after intubation, during pin placement, skin incision and duramater incision and total need for additional fentanyl were recorded. SPSS version 17 was used and data were analysed using Kruskal-Wallis or One-way ANOVA. Statistical significance was accepted at p < 0.05.Result: During craniotomy, heart rate, blood pressure, mean arterial pressure were significantly higher in patients without scalp block especially during pin placement. Statistical test showed significant difference, additional fentanyl in patients with scalp blocks was lesser, p = 0.000 (p <0.05). Conclusion: Levobupivacaine scalp block was effective to blunt hemodynamic response especially during pin placement. Scalp block also decreased additional fentanyl in craniotomy.


2010 ◽  
Vol 72 (5) ◽  
pp. 442-449 ◽  
Author(s):  
Jose M. Martinez ◽  
Amir Garakani ◽  
Horacio Kaufmann ◽  
Cindy J. Aaronson ◽  
Jack M. Gorman

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