The Pressor Response to the Drinking of Cold Water and Cold Carbonated Water in Healthy Younger and Older Adults

Purpose: Water drinking has been proposed for the treatment of orthostatic hypotension because it can increase blood pressure in patients. This study aimed to investigate whether drinking water with a cold or carbonation stimulus would cause a more effective pressor response, and whether it would be greater in older than in younger adults.Methods: We assessed blood pressure and heart rate from non-invasive arterial pressure (a volume-clamp method) and type II electrocardiography in 13 healthy young adults (6 females, 7 males; mean age, 19.9 ± 1.1 years) and nine healthy older adults (all females; mean age, 71.4 ± 4.2 years) who drank 200 mL of cold, cold carbonated, and room temperature water.Results: The pressor response to the drinking of cold and cold carbonated water was greater than that to room temperature water in both younger and older participants (p < 0.05; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in young: 15.31 ± 9.66, 22.56 ± 11.51 and 32.6 ± 17.98 mmHg, respectively; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in elderly: 21.84 ± 14.31, 41.53 ± 19.82 and 48.16 ± 16.77 mmHg, respectively). In addition, the pressor response to cold and cold carbonated water was persistent during the recovery period by about 5–10 mmHg (p < 0.05). Furthermore, the pressor response during the drinking and recovery periods was greater in the older than in the younger participants (p < 0.05).Conclusion: Our data suggest that even smaller amounts of water are able to elicit a sustained pressor response, in particular if the water is cold and carbonated. We speculate that the pressor effect may render cold and carbonated water an appropriate first aid method against certain forms of acute hypotension.

Endothelin Receptor Blockade Blunts the Pressor Response to Acute Stress in Obese Men and Women

Obesity is associated with dysregulation of the endothelin system. In obese individuals, an exaggerated pressor response to acute stress is accompanied by increased circulating endothelin-1. The impact of combined endothelin A/B receptor (ETA/B) antagonism on the stress-induced pressor response in overweight/obese individuals is unknown. Objective: To test the hypothesis that treatment with an ETA/B antagonist (bosentan) would reduce the stress-induced pressor response and arterial stiffness in overweight/obese compared to normal weight individuals. Methods: 40 participants [Normal weight (NW): n=20, BMI: 21.7 ± 2.4 kg/m2 & Overweight/obese (OB): n=20, BMI: 33.8 ± 8.2 kg/m2] were randomized to placebo or 125 mg of bosentan twice a day (250 mg total) for 3 days. Hemodynamics were assessed before, during, and after a cold pressor test (CPT). Endothelin-1 was assessed at baseline and immediately after CPT. Following a washout period, the same protocol was repeated with the opposite treatment. Results: The change from baseline in mean arterial pressure (MAP) during CPT following bosentan was significantly lower (p=0.039) in the OB group, compared to the NW group (OB: 28±12 vs LN: 34±15 mm Hg). Conclusions: These results suggest that ETA/B antagonism favorably blunts the pressor response to acute stress in overweight/obese individuals.

Comparative evaluation of sevoflurane and propofol to facilitate insertion of supra glottic airway device

: Propofol has been used since ages as induction agent to aid in insertion of Supraglottic airway devices however its side effects like hypotension, apnea and pain on injection do coexist. To avoid these side effects sevoflurane has been studied and well recognized because of its sweet smelling property. We conducted this study with primary aim to compare the insertion conditions such as no. of attempts for insertion, hemodynamic variations and awakening after surgery. The secondary aim was to note the adverse effects associated with Sevoflurane and propofol. We included sixty female patients of age 18-65 years graded as ASA I and II undergoing short gynecological procedures. Patients were induced with Sevoflurane 8% or IV Propofol 2mg/kg. Attempts for I-gel insertion, jaw relaxation, biting, coughing, gagging, laryngospasm and hemodynamic pressor response and awakening after surgery were noted.Induction time with Propofol is less compared to Sevoflurane. I-Gel insertion time with Sevoflurane and Propofol is insignificant (p value= 0.93). 25 patients in Group S and 27 patients in group P had very easy insertion of I-gel. 23 patients in Group S and 27 patients in Group P had relaxed jaw. None of the patients in both groups experienced laryngospasm. Propofol provided better conditions for I-gel insertion with manageable hypotension while the patients induced with Sevoflurane were hemodynamically more stable but the jaw relaxation was less as compared to that provided by propofol. Induction with 8% Sevoflurane by Vital Capacity Breath (VCB) technique can be an alternative for induction in high risk patients. Also the awakening from anaesthesia is faster with sevoflurane and is more suitable for patients demanding early discharge after day care surgeries.

A PROSPECTIVE RANDOMIZED STUDY TO EVALUATE THE ANALGESIC AND SEDATIVE EFFECTS OF FENTANYL AND MIDAZOLAM TO NALBUPHINE AND MIDAZOLAM IN PATIENTS UNDERGOING AWAKE FIBEROPTIC

Background- Awake nasal or oral flexible fiberoptic intubation (AFOI) is technique of choice in known or anticipated difficult airway . The main aim was to have calm and cooperative patient who can follow verbal commands while maintaining adequate oxygenation . In our study, we compared the analgesic and sedative effects of fentanyl and midazolam with nalbuphine and midazolam in patients undergoing awake fiberoptic intubationmore tolerable and comfortable for the patient but also to ensure optimal intubating conditions. Material and Methods– A prospective, randomized comparison study among patients between the age of 18 and 60yrs of either sex, with anticipated difficult airway . We compared the analgesic and sedative effects of fentanyl and midazolam with nalbuphine and midazolam in patients undergoing awake fiberoptic intubation. The primary objectives of our study were to observe the level of sedation, intubation score and OAS score after completion of procedure. The secondary objectives included assessment of patient comfort, intubation time, hemodynamic changes and complications. Results – We found that comfort score and intubation time were significant lesser in Group which received fentanyl and midazolam than Group which received nalbuphine and midazolam . (p<0.05). The intubation attempt was similar in both groups (P>0.05). Conclusion– we concluded that both regimens used in this study provided comparable intubating conditions, better sedation and analgesia was observed in group fentanyl for airway procedure events. Our study concluded fentanyl to be the drug of choice for blunting of pressor response in such patients.

Effect of ingesting a meal and orthostasis on the regulation of splanchnic and systemic hemodynamics and the responsiveness of cardiovascular α1-adrenoceptors

Background: Postprandial orthostasis activates mechanisms of cardiovascular homeostasis in order to maintain normal blood pressure (BP) and adequate blood flow to vital organs. The underlying mechanisms of cardiovascular homeostasis in postprandial orthostasis still require elucidation. Methods: Fourteen healthy volunteers were recruited to investigate the effect of an orthostatic challenge (600-head-up-tilt for 20 minutes) on splanchnic and systemic hemodynamics before and after ingesting an 800-kilocalorie composite meal. The splanchnic circulation was assessed by ultrasonography of the superior mesenteric and hepatic arteries and portal vein. Systemic hemodynamics were assessed non-invasively by continuous monitoring of BP, heart rate (HR), cardiac output (CO), and the pressor response to an intravenous infusion on increasing doses of phenylephrine, an α1-adrenoceptor agonist. Neurohumoral regulation was assessed by spectral analysis of HR and BP, plasma catecholamine and aldosterone levels and plasma renin activity. Results: Postprandial mesenteric hyperemia was associated with an increase in CO, a decrease in SVR and cardiac vagal tone, and reduction in baroreflex sensitivity with no change in sympathetic tone. Arterial α1-adrenoceptor responsiveness was preserved and reduced in hepatic sinusoids. Postprandial orthostasis was associated with a shift of 500 ml of blood from mesenteric to systemic circulation with preserved sympathetic-mediated vasoconstriction Conclusions: Meal ingestion provokes cardiovascular hyperdynamism, cardiac vagolysis, and resetting of the baroreflex without activation of the sympathetic nervous system. Meal ingestion also alters α1-adrenoceptor responsiveness in the hepatic sinusoids and participates in the redistribution of blood volume from the mesenteric to the systemic circulation in order to maintain a normal BP during orthostasis.

Sensory neuron inositol-1,4,5-trisphosphate (IP3) receptors contribute to chronic mechanoreflex sensitization in rats with simulated peripheral artery disease

The mechanoreflex is exaggerated in patients with peripheral artery disease (PAD) and in a rat model of simulated PAD in which a femoral artery is chronically (~72hrs) ligated. We found recently that, in rats with a ligated femoral artery, blockade of thromboxane A2 (TxA2) receptors on the sensory endings of thin fiber muscle afferents reduced the pressor response to 1 Hz repetitive/dynamic hindlimb skeletal muscle stretch (a model of mechanoreflex activation isolated from contraction-induced metabolite production). Conversely, we found no effect of TxA2 receptor blockade in rats with freely perfused femoral arteries. Here we extended the isolated mechanoreflex findings in "ligated" rats to experiments evoking dynamic hindlimb skeletal muscle contractions. We also investigated the role played by inositol 1-4-5-trisphosphate (IP3) receptors, receptors associated with intracellular signaling linked to TxA2 receptors, in the exaggerated response to dynamic mechanoreflex and exercise pressor reflex activation in ligated rats. Injection of the TxA2 receptor antagonist daltroban into the arterial supply of the hindlimb reduced the pressor response to 1 Hz dynamic contraction in ligated but not "freely perfused" rats. Moreover, injection of the IP3 receptor antagonist xestospongin C into the arterial supply of the hindlimb reduced the pressor response to 1 Hz dynamic stretch and contraction in ligated but not freely perfused rats. These findings demonstrate that, in rats with a ligated femoral artery, sensory neuron TxA2 receptor and IP3 receptor mediated signaling contributes to a chronic sensitization of the mechanically activated channels associated with the mechanoreflex and the exercise pressor reflex.

Abstract P198: Biphasic And Sex-dependent Roles Of The Prorenin Receptor In The Rostral Ventrolateral Nucleus In Mice Subjected To Deoxycorticosterone Acetate-salt Hypertension

The brain renin angiotensin system (RAS) regulates blood pressure (BP) and autonomic function. However, it remains unclear how and where angiotensin II (Ang II) is generated in conditions eliciting brain RAS overactivation including deoxycorticosterone acetate (DOCA)-salt hypertension (HT). In several tissues, the activation of prorenin requires its binding to the prorenin receptor (PRR). New evidence from this study indicates that prorenin and PRR are co-expressed in the proximity to the rostral ventrolateral nucleus (RVL), an anatomical brain region that controls sympathetic nerve activity. Therefore, we hypothesized that selective ablation of PRR targeting the RVL attenuates BP increase due to DOCA-salt. PRR ablation was targeted to the RVL by stereotactic microinjections of adeno-associated virus (AAV) expressing Cre recombinase-mCherry in PRR-flox mice (PRR RVL-KO ). AAV mCherry was used as control virus (WT). A pressor response to L-glutamate in the injection site served as confirmatory stereotactic target hit. RVL-targeted ablation of PRR resulted in lower BP responses to DOCA-salt in females (WT=115±3 vs KO=104±4 mmHg; p <0.05; n=8), but not males (n=5-8), only during the first 3 days of DOCA-salt treatment. However, at day 13 of DOCA-salt treatment, female PRR RVL-KO unexpectedly exhibited exaggerated increase in systolic BP (WT=149±3 vs KO=163±3 mmHg; p =0.004; n=8) and pulse pressure (WT=31±4 vs KO=45±4 mmHg; p =0.02; n=8) when compared to control. Next, mice were challenged with an intraperitoneal hypertonic saline injection equivalent to 10% of their body weight followed by 4 hours of urine collection. Urinary sodium excretion in female PRR RVL-KO was significantly lower when compared to WT ( p <0.05). These data indicate that the role of PRR in the RVL is sex-dependent and biphasic. That is, PRR contributes to the pressor response during the initial stage of DOCA-salt HT in females, presumably by facilitating the generation of angiotensin peptides in the RVL, while it plays a protective role by promoting renal sodium excretion and preventing elevation of systolic BP during the maintenance stage of DOCA-salt HT. This study suggests that distinct PRR expressing cell populations might elicit diverging physiological functions within the RVL.

Abstract 43: Non-Canonical AT1R/b-Arrestin2 Activation In Brain As A Regulator Of Fluid Homeostasis And Blood Pressure

The brain renin angiotensin system (RAS) is known for its role in cardiovascular and metabolic regulation. Angiotensin II (Ang II) is the major active product of the RAS, exerting most of its physiological effects through the angiotensin type-1 receptor (AT 1 R). Canonical or G-protein-mediated signaling of the AT 1 R within the brain has long been known to induce a dipsogenic and pressor response upon Ang II stimulation. Non-canonical or β-Arrestin mediated signaling is thought to counterbalance the detrimental effects of canonical signaling. However, the non-canonical AT 1 R/β-Arrestin pathway within the brain is understudied. Therefore, it is hypothesized that β-Arrestin activation contributes to fluid homeostasis and blood pressure (BP) regulation. Global β-Arrestin1 ( Arrb 1) and β-Arrestin2 ( Arrb 2) knockout (KO) mice were employed to evaluate drinking behavior and BP with and without deoxycorticosterone acetate (DOCA). Age- and sex-matched C57BL/6J mice served as controls. Mice were subjected to the two-bottle choice paradigm, in which the animals were presented with two bottles, one containing water and one containing 0.15M saline. In the absence of DOCA, mice lacking β-Arrestin2 had increased saline intake when compared to β-Arrestin1-KO and wildtype (WT=2.2±0.2 and Arrb 1-KO=2±0.4 vs Arrb 2-KO=5±0.7 mL/day; p<0.001; n=13, 11 and 9, respectively). This resulted in a saline preference, which means mice preferred saline over water by more than 50% by volume. In the presence of DOCA, mice lacking β-Arrestin2 had increased saline intake when compared to β-Arrestin1-KO and wildtype (WT=10.6±1.2 and Arrb 1-KO=6.5±0.8 vs Arrb 2-KO=16.6±2 mL/day; p<0.001; n=13, 11 and 9, respectively). However, these mice did not develop a saline preference. Preliminarily, β-Arrestin2-KO mice exhibited higher BP when compared to WT at baseline (WT=108±5 vs Arrb 2-KO=124±6 mmHg; n=2), which was exacerbated in response to DOCA (WT=122±6 vs Arrb 2-KO=140±5 mmHg; n=2). These findings suggest that β-Arrestin2 might counterbalance effects of canonical activation of the AT 1 R through G proteins. Overall, β-Arrestin2 appears to protect against cardiovascular diseases since the genetic ablation of β-Arrestin2 resulted in an increase in saline intake and exacerbated BP.

Abstract P184: Aging Male Offspring Of Polycystic Ovary Syndrome Rat Model Have Normal Blood Pressure And Exaggerated Pressor Response To Angiotensin II

Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenemia and elevated blood pressure (BP). Male offspring of hyperandrogenemic female (HAF) rats, PCOS model, have low birth weight, with normal BP, but exaggerated pressor response to Angiotensin (Ang) II as adults. The present study tested the hypothesis that with aging, male HAF offspring are at increased risk of developing hypertension (HT). Methods: Hyperandrogenemia was induced in female SD rats (5α-dihydrotestosterone pellets 7.5 mg/90 d, s.c. at 4 wks of age and throughout life). HAF and controls (10-12 wks of age) were mated, allowed to deliver and lactate. HAF and control male offspring (F1 HAF and F1 Contr. ) were left untreated until 16-20 mos of age. Body composition (echoMRI) and proteinuria were measured in aging offspring. BP was measured (baseline; 9 d, enalapril (25 mg/kg/d); 7d) by telemetry. Rats were then given Ang II (50 ng/kg/min, s.c. minipumps) or saline (No Ang II) for 13 d. High salt (4%) diet (HSD) was started for both Ang II and No Ang II groups on day 8 of Ang II. Results: Aging male F1 HAF had similar fat mass, but lower lean mass (433.7 ± 6 vs 453.6 ± 7 g, p< 0.05) and body weight (552.3 ± 11 vs 590.4 ± 11 g, n = 8-16, p<0.05) than F1 Contr. . Despite higher proteinuria in F1 HAF (412 ± 42 mg/24h vs 292 ± 47 mg/24h, n = 11-13, p<0.05), baseline mean arterial pressure (MAP) was similar between F1 HAF and F1 Contr. (130 ± 1 mmHg vs 126 ± 4 mmHg, respectively, n = 8, p=NS). Enalapril decreased MAP similarly in both F1 HAF and F1 Contr. (110 ± 2 mmHg vs 107 ± 3 mmHg, respectively). On low salt, Ang II increased MAP to higher levels in F1 HAF than F1 contr., saline-treated>F1 HAF and F1 Contr. (140 ± 11 mmHg vs 119 ± 10 mmHg, 105 ± 3 mmHg and 103 ± 4 mmHg, respectively, n = 4, p<0.05 F 1 HAF vs other grps). With 6 days of HSD, MAP was similar between F1 HAF and F1 Contr. not treated with Ang II (142 ± 6 mmHg and 132 ± 9 mmHg, respectively). MAP was also similar between F1 HAF and F1 Contr. with Ang II (169 ± 1 mmHg and 159 ± 9 mmHg, respectively). However, both Ang II-treated groups had significantly higher MAP compared to their respective No Ang II control groups. Conclusion: Aging male HAF offspring do not develop hypertension, but are at increased risk of renal injury and cardiovascular disease due to enhanced pressor sensitivity to Ang II.