bluuebunny/crossref_metadata_2025 huggingface dataset:
TAS2R50 genotype and dietary preferences
Authors: Asik Christine , Eny Karen , Herd Sarah , Lee Hyeon Joo , El‐Sohemy Ahmed
Published: June 2021

The TAS2R50 gene belongs to the TAS2R taste receptor family, which mediate bitter taste perception. The objective of this study was to determine if genetic variation in TAS2R50 is associated with differences in dietary preferences. Individuals (n=967) between the ages of 20 and 29 years completed a food preference checklist to rank their liking/disliking of 24 bitter foods and beverages on a 9‐point scale. Subjects who reported the lowest 3 points were classified as disliking. DNA was isolated from blood samples and genotyped for a polymorphism in TAS2R50 (rs2900554, G>T). In this population, the frequency of the G and T alleles were 36.8% and 63.2%, respectively. The TAS2R50 genotype was strongly associated with different preferences for grapefruit and grapefruit juice. Individuals with the GG genotype were most likely to report disliking grapefruit followed by individuals with the GT and TT genotypes (30.0%, 15.8%, 7.8%; p<0.0001). Similar effects were observed for grapefruit juice (33.3%, 18.7%, 14.9%; p<0.0001). TAS2R50 genotypes were also associated with differences in preference for kale (p=0.008), spinach (p=0.01), turnip (p=0.03) and bitter sweet chocolate (p=0.05). These results indicate that common variations in the TAS2R50 gene are associated with differences in preference for grapefruit and other bitter tasting foods and may explain inter‐individual differences in the consumption of these foods.

Grant Funding Source

The Advanced Foods and Materials Network
Effects of Ethanol on Sleep and Central Respiratory Motor Activity
Authors: Vecchio Laura Marie , Liu Hattie , Harding Stephen , Le Anh , Horner Richard
Published: June 2021

Ethanol worsens sleep‐disordered breathing in humans. To determine whether this effect may be due to a central depression of respiratory motor activity and/or sedation, we recorded sleep‐wake states, genioglossus and diaphragm muscle activities in freely‐behaving rats (n=10), following intra‐peritoneal injection of 1.25 g/kg ethanol or saline (control) in random order. Ethanol injections resulted in maximum blood levels of 140 mg/dl, i.e., a physiologically relevant level for producing impairment of cognitive and motor behavior in rats and humans. Ethanol decreased wakefulness (P=0.03), increased non‐rapid eye movement (NREM) sleep (P=0.02) but had no effect on REM sleep (P=0.81). Ethanol also decreased respiratory‐related genioglossus activity in wakefulness (P=0.02), but not diaphragm amplitude or respiratory rate in any state. However, application of ethanol in doses ranging from 0.025 to 1 M directly to the hypoglossal motor nucleus in isoflurane‐anesthetised rats (n=10) did not suppress genioglossus muscle activity. In conclusion, ethanol at physiologically relevant concentrations promoted sleep indicative of a sedating effect. The lack of effect on genioglossus muscle activity with ethanol applied directly to the hypoglossal motor nucleus suggests that the suppression observed with systemic administration was mediated via effects operating outside this motor pool.

Supported by: CIHR
Brain Derived Neurotrophic Factor (BDNF) blunts neural activity in the nucleus tractus solitarius (nTS)
Authors: Clark Catharine Grace , Hasser Eileen M. , Kunze Diana L. , Katz David M. , Kline David D.
Published: June 2021

The nTS is the principal relay for cardiorespiratory sensory input to the brainstem and thereby plays critical roles in autonomic homeostasis. BDNF and its receptor, TrkB, are expressed in nTS, and BDNF inhibits glutamatergic AMPA receptors in dissociated nTS relay neurons (Balkowiec, et al., 2000). To further define the role of BDNF in regulating activity of nTS neurons, we used patch clamp recording from (4 weeks) rat brainstem slices to compare excitatory postsynaptic currents (EPSCs) and action potentials (APs) in the absence and presence of BDNF (100 ng/mL) or a BDNF blocking antibody (antiBDNF, 10 ug/mL). BDNF (n=7) reduced the frequency of spontaneous EPSCs (sEPSC, cntl: 9.1 ± 1.0 Hz vs. BDNF: 6.3 Hz ± 0.7, p=0.003), whereas antiBDNF increased sEPSC frequency (cntl, n=11: 8.0 ± 1.0 Hz vs. antiBDNF, n=9: 17.1 ± 4.7 Hz, p=0.05). Neither treatment altered sEPSC amplitude. Stimulation of the solitary tract at 0.1, 0.5 and 20 Hz evoked low jitter EPSCs (0.298 ±0.06 µs) that were reduced in amplitude by application of BDNF (n = 3). BDNF also reduced input resistance (cntl: 584.1 ± 163.9 vs BDNF: 243.6 ± 55.7 MOhm, p=0.03, n=6) and, in a subset of neurons, the number of APs evoked by current injection (500 ms, 10 pA steps; p < 0.05). These findings demonstrate that activity of neurons in nTS is subject to modulation by exogenous and endogenous BDNF and suggest that BDNF may have both pre‐ and post‐synaptic sites of action. NS057398 (DMK)
Anatomical location and electrophysiological properties of the serotonin receptors type 2 (5‐HTR2) in the nucleus of the solitary tract (nTS).
Authors: Austgen James R , Dantzler Heather A , Kline David D
Published: June 2021

Serotonin plays a major role in cardiorespiratory function in health and disease. While 5‐HTR2 is believed to be excitatory, its location, function and mechanism of action in the nTS requires clarification. We determined the location and electrophysiological properties of 5‐HT and 5‐HT2R subtypes in the nTS. In immunohistochemical studies, nTS sections where treated with antibodies against 5‐HTR2A, ‐2B and ‐2C. The synaptic vesicle marker synaptophysin was used to identify synaptic terminals. nTS neurons were recorded using the patch clamp technique in the slice preparation. Spontaneous and solitary tract‐evoked excitatory postsynaptic currents (s/eEPSC) and current‐induced action potential discharges (APD) were recorded. 5‐HT2 receptor subtypes displayed distinct immunoreactivity: 5‐HTR2A in fibers and cell bodies; 5‐HTR2B in the cell soma; 5‐HTR2C in fiber‐like processes. A fraction of 5‐HT2C immunoreactivity co‐labeled with synaptophysin. Electrophysiological recordings of nTS neurons showed an increase in the frequency of sEPSCs with 5‐HT (10 μm, 15.3 ± 2.5 vs. 47.1 ± 8.3 Hz, p<0.05). α‐methyl 5‐HT (a general R2 agonist, 10 μm) decreased the amplitude of sEPSC (‐21.9 ± 1.2 vs. ‐14.9 ± 0.8 pA). Application of a 2B agonist (BW 723C86, 10μm) reduced current injected‐APD. This information suggests that 5‐HTR2 subtypes are located in the NTS and have a roll in synaptic function. HL085108 (DDK)
Collecting duct‐specific Rh C Glycoprotein deletion alters basal and acidosis‐stimulated renal ammonia metabolism
Authors: Lee Hyun‐Wook , Verlander Jill W. , Bishop Jesse , Igarashi Peter , Handlogten Mary E. , Weiner I. David
Published: June 2021

Renal collecting duct NH3 secretion is a key element of acid‐base regulation and has been attributed to passive diffusion. Mammalian Rh Glycoproteins are similar to Mep/Amt ammonia transporters in other organisms.[jvr1] Rh C Glycoprotein (Rhcg) is expressed in the collecting duct. To determine if the collecting duct secretes NH3 via Rhcg, we generated mice with collecting duct‐specific Rhcg deletion (KO), which we confirmed by immunohistochemistry. KO mice had loxP sites in introns 4 and 9 of the Rhcg gene (Rhcgfl/fl) and expressed Cre‐recombinase under control of the Ksp‐cadherin promoter (Ksp‐Cre). Control (C) mice were Rhcgfl/fl but Ksp‐Cre‐negative. Basal urinary ammonia excretion was less in KO vs C mice (71±9 vs 94±6 μmol d−1, n=8 and 6, p<0.05). In mice acid‐loaded by adding 0.4M HCl to normal rodent chow, day 1 urinary ammonia excretion did not change significantly in KO mice (Δ=‐16±19 μmol d−1, n=6, p=NS), whereas it increased significantly in C mice (Δ=154±37 μmol d−1, n=6, p<0.005). Urinary ammonia excretion was significantly less in KO vs C mice each subsequent day. After 7 days, metabolic acidosis, measured as serum [HCO3−], was more severe in KO than C mice (16.2±1.0 vs 20.5±0.8 mmol/L, p<0.02, n=6 and 5). Other differences between acid‐loaded KO and C mice included lower urine pH at day 2 and decreased glutamine synthetase and increased PEPCK and Rhbg expression at day 7 in KO mice. We conclude: 1) collecting duct ammonia secretion is, at least in part, mediated by Rhcg and not due solely to passive NH3 diffusion; and 2) during metabolic acidosis compensatory responses to Rhcg deletion contribute to partial increases in ammonia excretion.

This work was supported by NIDDK.
SIGNALING PATHWAYS INVOLVED IN THE INHIBITORY EFFECT OF UROGUANYLIN ON RENAL NHE3 AND H+‐ATPase
Authors: Lessa Lucilia Maria Abreu , Lacroix Luciene Carraro , Fonteles Manassés Claudino , Malnic Gerhard
Published: June 2021

Uroguanylin (UGN) is a peptide synthesized in intestine that modulates sodium balance through actions on the kidney. In the present work we investigated the signaling pathways involved in the UGN action on H+ secretion in rat renal tubules and in LLC‐PK1 and MDCK‐C11 cells. Measuring H+ secretion through stationary microperfusion, the inhibitory effect of UGN on HCO3− reabsorption was abolished by KT5823 (PKG inhibitor) in rat proximal (JHCO3−,nmol.cm−2.s−1: 2,4±0,26control x 1,56±0,21UGN P<0,05; 2,06±0,09KT x 2,14±0,15KT+UGN P>0,05) and in distal tubules (JHCO3−: 0.86±0,12control x 0.51±0,07UGN P<0,05; 0.77±0,05KT x 0.87±0,07KT+UGN P>0,05). In the in vitro studies we used fluorescence microscopy to measure intracellular pH (pHi), utilizing BCECF as H+ sensitive dye. In LLC‐PK1 cells, UGN reduced NHE3 activity in the presence of 500nM HOE (NHE1 inhibitor). This effect was reduced by KT5823 and abolished by H89 (PKA inhibitor). 8br‐cGMP (cGMP analogue) mimicked the effects promoted by UGN in both rat proximal tubules and LLC‐PK1 cells. In MDCK‐C11 cells, UGN inhibited the H+‐ATPase activity in the presence of Schering (H/K‐ATPase inhibitor) and EIPA (NHE inhibitor). The PKG is also involved in this effect of UGN. These results demonstrate that UGN inhibits H+ extrusion via NHE3 and H+‐ATPase, and that this effect involves the activation of PKG and PKA pathways, suggesting a crosstalk between these pathways.
GLUCOSE EFFECT ON NHE3 ACTIVITY AND SIGNALING PATHWAY IN THE PROXIMAL TUBULE OF NORMAL, STREPTOZOTOCIN‐INDUCED DIABETIC AND PHLORIDZIN TREATED RATS
Authors: Pessoa Thaíssa Dantas , Malnic Gerhard
Published: June 2021

The effects and signaling pathways of glucose on NHE3 activity in proximal tubule of Wistar rats were studied using the stationary microperfusion technique to measure H+ secretion. Glucose 5mM perfusion stimulated HCO3− reabsorption compared to perfusion without Glucose plus SGLT inhibitor Phloridzin (0,5 mM) (JHCO3−, nmol.cm−2.s−1 ‐ 2,87±0,25 G 5mM x 0,89±0,11Phloridzin). High glucose (20mM) perfusion had an intermediary effect (JHCO3−‐ 1,84±0,0,25). Glucose 5mM with p38MAP‐Kinase inhibitor PD169316 and PI3‐Kinase inhibitor LY294002 perfusion abolished the stimulatory effect of Glucose 5 mM. H+ secretion, Na+ and K+ fractional excretion (FE) and glomerular filtration rate (GFR) were also investigated in streptozotocin‐induced diabetic rats and phloridzin‐treated rats to determine if chronic stimuli or inhibition of SGLT 1 had an effect on NHE3 activity and renal function. Diabetic animals showed an 66% increase of NHE3 activity (during 20 mM glucose perfusion) as well as K+ and Na+ FE compared with non treated animals, and a reduction of 85% on K+ FE with chronic Phloridzin treatment. In conclusion, 5 mM Glucose perfusion had a higher stimulatory effect on NHE3 activity than high glucose (20 mM) in controls and the p38MAPKinase and AKT pathways are involved in this signaling effect. Diabetic animals had increased NHE3 activity during 20 mM glucose perfusion.
Chronic Angiotensin II Infusion in Lewis Rats Does Not Reveal Sex Differences in Blood Pressure or Renal Injury Apparent in the mRen2.Lewis Strain
Authors: Diz Holland , Pendergrass Karl , Westwood Brian , Chappell Mark
Published: June 2021

Sexual dimorphism in blood pressure is evident in hypertensive mRen(2).Lewis (mRen2), but not the normotensive Lewis rat. As circulating and renal angiotensin II (Ang II) levels are higher in male mRen2, we determined whether Ang II infusion (300 ng/kg/min, osmotic minipump, 2 wks) would also reveal sex differences in pressure and proteinuria in male (M) and female (F) Lewis rats, as well as in ovariectomized (OVX) females. Ang II infusion significantly elevated systolic blood pressure in all groups (157 + 4, n=18 M/F/OVX vs. 112 + 1 mm Hg, n=10 M/F); however, pressure was not different between groups. Proteinuria was also comparable between the male and female Lewis rats following Ang II (M: 3.5+0.6; F: 4.0 +0.9 mg/mg creatinine), but was reduced in the OVX Lewis (0.7+0.2 mg/mg creatinine, p<0.05). Kidney angiotensin content was not different for Ang II or Ang‐(1‐7) in the renal cortex; however, medullary Ang II levels were lower in the OVX Lewis (OVX: 0.37+0.03; F: 0.66+0.16; M: 0.94+0.10 fmol/mg) while Ang‐(1‐7) content was higher in the female groups (OVX: 5.2+0.4; F: 5.3+0.3; M: 3.9+0.3 fmol/mg). In summary, chronic Ang II infusion in Lewis rats does not replicate the sex differences in pressure or proteinuria evident in the mRen2 strain. OVX increases blood pressure in the mRen2, but does not exacerbate pressure in female Lewis emphasizing key differences between models of Ang II infusion and genetic activation of the RAS.
Aldosterone modulates hormone receptor binding to unique elements in the endothelin‐1 (ET‐1) promoter
Authors: Stow Lisa R , Gumz Michelle L , Lynch I Jeanette , Greenlee Megan M , Cain Brian D , Wingo Charles S
Published: June 2021

We previously identified ET‐1 as an aldosterone‐induced gene in inner medullary collecting duct (IMCD) cells. These hormones exert opposing action on renal sodium transport, and this interaction may represent the first known negative feedback loop on renal aldosterone signaling. In these studies we verified the interaction in rat; aldosterone stimulated ET‐1 mRNA in IMCD ex vivo and ET‐1 peptide in inner medulla in vivo. We mapped 2 unique hormone response elements (HREs) in the ET‐1 promoter and confirmed mRNA stimulation occurred by transcription. RNA silencing corroborated pharmacological data and showed aldosterone utilized both mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in this response. Notably, ET‐1 mRNA stimulated by a small physiological aldosterone dose (10 nM) was accompanied by nuclear translocation and direct binding of MR and GR to ET‐1 HREs. Aldosterone, but not competitive inhibitors, recruited coactivators, modified histones and RNA polymerase II to the ET‐1 promoter. In summary, aldosterone action on ET‐1 occurs in vivo, involves novel MR/GR cooperation at unique HREs, and may mediate crucial negative feedback on aldosterone action. Supported by NIDDK and AHA.
Splenic reflex neurohormonal modulation of mesenteric arterial diameter and blood flow
Authors: Hamza Shereen M , Kaufman Susan E
Published: June 2021

Portal hypertension (PH) increases splenic venous pressure and alters splanchnic hemodynamics. We have shown that elevated splenic venous pressure results in a reflex increase in splenic afferent and mesenteric efferent nerve activity. We hypothesized that this neural reflex increases mesenteric arterial tone. In male rats, splenic venous pressure was selectively elevated by partial splenic vein occlusion (SVO). This caused a drop in superior mesenteric arterial blood flow (‐2.0±0.6 mL/min, n=6) which was abolished by splenic denervation (‐0.65±0.3 mL/min, n=5, p<0.05). In separate animals, mesenteric resistance arteries (40‐70μm) were directly visualized with intravital microscopy. Immediately following SVO, mesenteric arterial diameter fell (‐3.1±1.1μm, n=13); this was abolished by splenic denervation (+0.3±0.5μm, n=10, p<0.05), renal denervation (+1.4±0.6μm, n=4, p<0.05) and the angiotensin II AT1 receptor blocker Losartan (+0.45±0.2μm, n=6, p<0.05). Interestingly, mesenteric denervation only attenuated this effect (‐0.2±0.4µm, n=7, p=0.048). We propose that mesenteric arterial tone is modulated primarily by splenorenal reflex mediated release of angiotensin II, with possible contribution from mesenteric angiotensinergic nerves. This initial mesenteric arterial vasoconstriction has implications for initiation of the hyperdynamic circulation of PH. CIHR, AHFMR
Regulation of sympathetic nerve activity and arterial pressure by the rostral ventrolateral medulla in obese Zucker rats.
Authors: Huber Domitila Augusta , Schreihofer Ann Marie
Published: June 2021

Adult obese Zucker rats (OZR) have elevated sympathetic nerve activity (SNA) and arterial pressure (AP) with exaggerated sympatho‐excitatory responses (somatic and diving reflex) compared to lean Zucker rats (LZR). The present study sought to determine whether the altered control of SNA and AP in OZR could be due to enhanced glutamatergic or reduced GABAergic control of the rostral ventrolateral medulla (RVLM). Adult rats (14‐17 wks) were anesthetized with urethane (1.5 g/kg, iv), ventilated, and paralyzed for recording of SNA and AP. Microinjections of glutamate (1 nmol/100 nl) were performed into the RVLM to locate sites for maximal increases in SNA and AP (1.4 ‐ 1.8 mm rostral to calamus, 1.7 ‐ 2.1 mm lateral to midline, 2.7 ‐ 3.1 mm ventral; tip angled 20° rostrally). Baseline mean AP of OZR was significantly higher than LZR (n=6, 124 ± 2 mmHg in OZR vs n=6, 108 ± 6 mmHg in LZR, P<0.05). The OZR had larger maximal increases in AP (n=6, 30 ± 3 mmHg in OZR vs n=6, 20 ± 2 mmHg in LZR, P<0.05) and SNA (n=6, 74 ± 8 % of baseline in OZR vs n=6, 58 ± 8 % in LZR) than LZR. After the blockade of GABAA receptors in the RVLM (gabazine; 100 pmol/100nl) the increases in AP (n=6, 58 ± 11 mmHg in OZR vs n=6, 42 ± 7 mmHg in LZR) and SNA (n=6, 83 ± 17 % of baseline in OZR vs n=6, 84 ± 21 % in LZR) were similar between groups. These results suggest that the RVLM is more easily activated by glutamate, but that tonic GABAergic inhibition of the RVLM is not altered in OZR compared to LZR.

Grant Support: NIH R01HL086759
TrkB pathway may mediate NR1 phosphorylation in the supraoptic nuclei following dehydration in the rat
Authors: Carreño Flávia Regina , Ji Lisa , Cunningham J Thomas
Published: June 2021

Osmotic stimulation increases brain derived neutrophic factor (BDNF) release and mRNA expression in the supraoptic nucleus (SON). However, the significance of BDNF and its receptor TrkB in the regulation of vasopressin secretion remains to be determined. Brain punches that contained the SON were collected from euhydrated controls, 48 h water deprived rats (48WD), and two other groups of rats were water deprived for 46 h followed by access to water for 2 (2hR) or 4 h (4hR). Punches were homogenized and the total lysate was subjected to Western Blot analysis for TrkB, NR1 and NR2 subunits and phosphorylated forms of TrkB (pTrkBY515) and NR1 (pNR1) expression. Densitometric measurements of the immunoreactive bands were normalized using GAPDH. Although no changes were observed for TrkB, NR1, and NR2 expression, pTrkBY515 and pNR1 expression were significantly increased (P<0.01) in the SON of 48hWD animals compared to euhydrated animals. NR2 phosphorylation was not affected. Accesses to water for 2 h reduced pTrkBY515 without effecting pNR1. Finally, 4 h rehydration decreased pTrkBY515 to control levels and reduced pNR1 expression. In conclusion, our data suggest that increased TrkB phosphorylation in the SON following dehydration may play a role in the upstream phosphorylation of NR1. TrkB signaling in the SON may affect cellular excitability and vasopressin release during progressive dehydration. NIH R01, HL62579
Chronic Aortic Barodenervation switches salt‐sensitive normotension to salt‐sensitive hypertension in rats
Authors: Rodríguez‐Martínez Manuel , Rodríguez‐Pérez Adriana S. , López‐ Rodríguez Juan F. , Calvo‐Turrubiartes Miriam Z.
Published: June 2021

Our prior (EB08 Abs.738.4) cross sectional study suggested that bilateral chronic aortic baroreceptor denervation (AD) induces salt‐sensitive normotension in rats. To assess this in depth, mean arterial pressure (MAP) was measured intra‐arterially over time (3 times) in two groups of conscious Wistar rats. The first time (PreDen) was measured in caudal artery before random sham (SH, n = 7) or real AD (n = 10); the second one was measured in left femoral artery after 7 days on low sodium diet (PostDen LNaD = 0.04% Na) and the third time was measured in right femoral artery after 21 days on high sodium diet (PostDen HNaD = 8% Na). The effectiveness of AD was judged by Box‐Cox transformation of PHE(1) and SNP (2) slope [((( [3 ‐ (HR2‐HR1/ MAP2‐MAP1)] −0.4) ‐1) / ‐0.046)] obtained in conscious state. Salt Sensitivity = SS = (PostDen HNaD MAP ‐ PostDen LNaD MAP, mmHg). Delta of MAP (PostDen MAP ‐ PreDen MAP, mmHg) on both LNaD and HNaD were calculated too. &p = 0.05, *p <0.003 vs SH and + p < 0.01, # p < 0.009 vs LNaD.

PreDen PostDen PostDen SS Delta MAP DeltaMAP

LNaD HNaD LNaD HNaD

SH 105.0 114.0 122.0+ 7.7 9.0 16.7+

±2.7 ±1.8 ±1.7 ±2.5 ±2.6 ±2.3

AD 101.0 123.2& 134.5*# 11.3 22.2* 33.5*#

±2.0 ±2.4 ±2.8 ±2.6 ±2.0 ±2.4

Conclusions

Wistar rats show salt‐sensitive normotension that chronic AD switches to salt‐sensitive hypertension. Supported by: CONACYT 62282
Acute and Chronic Stressors Differentially Affect Myogenic Reactivity of Mesenteric Arteries in Spontaneously Hypertensive Male Rats
Authors: Reho John J , Peck Jennifer , Ramirez Rolando J , Dunphy Gail , Boehme Shannon , Ely Daniel
Published: June 2021

Acute and chronic stressors contribute differentially to the development of cardiovascular diseases involving blood pressure, vessel reactivity, and stress hormones. To investigate these mechanisms, we used restraint (acute ‐ 1 hr) and colony environmental housing (chronic ‐ 3 months) to examine changes in: systolic blood pressure (SBP), vessel reactivity to intraluminal pressure increases (myogenic reactivity, MYO), and plasma norepinephrine (NE) as an index for sympathetic nervous system (SNS) activity. We hypothesized that acute restraint stress will increase SBP, MYO of resistance‐sized mesenteric arteries, and plasma NE more compared to chronic environmental stress. Age‐matched adult SHR males were subjected to weekly restraint stress (n=7; 3 days/wk ‐ 1 month) or continuous colony housing stress (n=9) as compared to non‐stressed controls (n=7) in standard caging. Blood pressure was measured weekly via tail cuff, mesenteric artery reactivity was determined using a pressurized arteriograph, and plasma NE was assayed by HPLC. Acute restraint stressed animals exhibited increased MYO of mesenteric arteries compared to chronically stressed and control animals (p<0.05) possibly due to physiological adaptation in the colony housed rats. In conclusion, acute restraint stress may lead to increased SNS activity that results in increased MYO of resistance vessels involved in regulating blood pressure.
Increases in blood pressure occur prior to significant elevations in weight in a diet‐induced life‐long obesity rat model
Authors: Northcott Carrie A , Haywood Joseph R , Dorrance Anne M
Published: June 2021

Obesity is at epidemic proportions, impacting both adults and children resulting in various health complications, including hypertension. We hypothesized that juvenile rats fed a high fat diet (HF) from weaning would have elevated blood pressure. Male Sprague Dawley rats were fed either HF or normal chow (NC) diets from 3 weeks of age. At four weeks animals had femoral arterial radiotelemetry transmitters implanted for mean arterial pressure (MAP) and heart rate (HR) measurements for 17 weeks. [DA1]After 2 weeks on the HF diet there was a significant increase in MAP compared to NC rats (95 + 1 vs. 92 + 1 mm Hg; p<0.05); the difference in blood pressure between the HF and NC rats increased throughout the study. Interestingly, it wasn't until 10 weeks of HF and NC diet that the body weight significantly differed (370 + 6 vs. 343 + 6 grams; p<0.05). At the conclusion of the study HF rats had significantly greater MAP (127 + 2 mm Hg) and body weight (471 + 5 g) compared to NC rats (113 + 3 mm Hg) (416 + 10g). MAP fall in response to ganglionic blockade was also slightly lower in HF compared to NC rats (p=0.07). In conclusion, elevations in MAP in response to a HF diet precede significant increases in body weight. Further studies will clarify the mechanism by which the increase in MAP prior to the weight gain occurs.
Effects of Digoxin‐binding Fab in a Rat Model of Preeclampsia
Authors: Agunanne Enoch , Horvat Darijana , Uddin Mohammad N , Puschett Jules
Published: June 2021

Objective

To investigate the effects of Digibind® (D, digoxin immune Fab, bovine) in the treatment of preeclampsia (PE) in a rat model. D inhibits the cardenolides and may have cross‐reactivity with the bufodienolides.

Methods

We induced PE in rats by administering DOCA and replacing their drinking water with 0.9% saline. D (10mg/kg) was given intraperitoneally on days 10‐21 of pregnancy (PDS‐D rats, n= 9). These were compared to PDS rats that received no D. (PDS, n=8) and normal pregnant rats (NP, n=10).

Results

The mean initial blood pressure (BP) was 111 ± 2, 101 ± 3, 104 ± 2 mmHg respectively for PDS‐D, PDS, NP. There was no statistical difference between PDS and NP initial BP. The final BP was 102 ± 1, 154 ± 3, 93 ± 4 mmHg respectively for PDS‐D, PDS, NP, (p < 0.001 PDS vs. NP and PDS vs. PDS‐D). The mean 24 hour protein excretion on day 21 was 2.4 ± 0.8, 5.4 ± 1.0, 2.3 ± 1.2 mg/24 hours, respectively for PDS‐D, PDS, NP, (p< 0.001 PDS‐D vs. PDS). The mean number of pups/litter was 12.8 ± 2.8, 11.5 ± 1.2, 14.9 ± 1.9 respectively for PDS‐D, PDS, NP (p < 0.05 PDS‐D vs. NP). Also, about 30% of the PDS‐D pups showed developmental retardation, compared to the NP indicating intrauterine growth restriction (IUGR).

Conclusions

D produced significant lowering of the blood pressure and proteinuria in a rat model of PE. However, teratogenic effects and IUGR were also observed in the PDS‐D group.

Scott, Sherwood/Brindley Foundation
Angiotensin II receptor expression and blood pressure in F1 generation SHR‐Brown Norway congenic rats
Authors: Patterson Elaine , Kretzer Julie , Crutcher Rebecca , Collett Jason , Bradshaw Timothy , Osborn Jeffrey
Published: June 2021

Angiotensin II type 1 receptor (AT1r) expression is increased in genetic models of hypertension including the Okamoto Spontaneously Hypertensive Rat (SHR). This study evaluated tissue AT1r expression compared to arterial blood pressure of F1 generation offspring of SHR female crossed with Brown Norway (BN) male rats. Systolic and diastolic arterial pressures were measured by tail cuff plethysmography and mean arterial pressure (MAP) was calculated. Offspring were sacrificed at 15‐20 weeks of age and tissues were rapidly frozen for analysis of AT1r. MAP of parent, female SHR was 151 mmHg and parent male BN was 94 mmHg. F1 generation offspring were produced from 6 separate matings of SHR and BN parents. Blood pressures of F1 offspring were measured at 14‐17 weeks of age. F1 progeny were grouped according to borderline hypertension (BHT; MAP < 122 mmHg; n=18) and hypertension (HT; MAP > 122 mmHg; n=15). All progeny exhibited MAPs greater than 107 mmHg. Total tissue protein was extracted from forebrain, hypothalamus and kidney tissues and separated by gel electrophoresis. Western blot analysis was conducted for AT1r. In F1 SHR/BN, there were no detectable differences in AT1r between BHT and HT animals. Hypertension in SHR is dominantly expressed when crossed with NT‐BN. The data suggest that differences in MAP of F1 BHT and HT SHR/BN are not mediated by altered AT1r expression. (Supported by UK Biology Ribble Foundation)
DOCA‐salt hypertensive rats display decreased vascular reactivity to urotensin‐II
Authors: Carneiro Fernando Silva , Carneiro Zidonia Nunes , Giachini Fernanda Regina Casagrande , Lima Victor V , Webb R Clinton , Tostes Rita C
Published: June 2021

Introduction

Urotensin‐II (U‐II) is a vasoconstrictor peptide and its potency can be up to 100 fold greater than that of endothelin‐1 (ET‐1). ET‐1 plays a major role in the vascular changes associated with salt‐sensitive hypertension, but the effects of U‐II in arteries from these animals have not yet been defined.

Objective

We hypothesized that DOCA‐salt rats have increased vascular reactivity to U‐II.

Methods and Results

Wistar rats were unilaterally nephrectomyzed and deoxycorticosterone‐acetate (DOCA) (200mg/Kg) pellets were implanted. DOCA rats received water containing 1% NaCl/0.2% KCl, for 5 weeks. Aortic rings were mounted in myograph chambers and functional studies were performed. DOCA rats displayed increased systolic pressure (Control: 117±1 vs DOCA: 179±3; mmHg). Maximal contractions (mN) to U‐II were decreased in endothelium‐intact (Control: 16.6±1 vs DOCA: 8.8±1) and endothelium‐denuded (Control: 21.3±1.1 vs DOCA: 10.4±0.9) aortas from DOCA rats. This difference was abolished in endothelium‐intact vessels incubated with 10−5M urantide (U‐II antagonist) (Control: 13.5±0.9 vs DOCA: 12.7±0.9).

Conclusion

Our results suggest that U‐II production/release is augmented in mineralocorticoid hypertension and that decreased vascular reactivity to the peptide may represent counter‐regulatory mechanisms that limit additional vascular damage to this potent vasoconstrictor.
Induction of hemeoxygenase‐1 slows the progression of hypertension and proteinuria in spontaneously hypertensive rats
Authors: Elmarakby Ahmed A. , Foster Jan M. , Sullivan Jennifer C.
Published: June 2021

The renoprotective mechanisms of hemeoxygenase‐1 (HO‐1) induction remain unclear. We hypothesize that induction of HO‐1 will decrease blood pressure and proteinuria in spontaneously hypertensive rats (SHR) via antioxidant and anti‐inflammatory mechanisms. Male WKY and SHR were injected with the HO‐1 inducer cobalt protoporphrin (CoPP, 1.5 mg/kg s.c. bi‐weekly) for two weeks. CoPP reduced mean arterial pressure (MAP) (133±2 vs. 144±4 mmHg, p<0.05) and proteinuria (24±2 vs. 14±1mg/day, p<0.05) in SHR rats compared to baseline values, with no effect in WKY. Renal cortical superoxide (O2−) production and urinary 8‐isoprostane excretion were higher in SHR compared to WKY (O2−: 10.5±1 vs.6±1 CPM/mg protein, p<.05; 8‐iso: 7±1.3 vs. 3.4±0.8 ng/day, p<0.05) and CoPP attenuated oxidative stress levels in SHR only (O2−: 5.1±1 CPM/mg, p<0.05; 8‐iso: 4.4±0.7 ng/day). SHR showed a marked elevation in urinary MCP‐1 excretion compared with WKY (19±2 vs. 7.5±2.5 ng/day, p<0.05) and this was attenuated by induction of HO‐1 in SHR (10.5±2.7 ng/day). Plasma nitrite was reduced in SHR compared to WKY (7.9±1.1 vs. 12.7±1.5 μM, p<0.05) and HO‐1 induction increased plasma nitrite levels in SHR (17.5±2.9 μM). These data demonstrate that induction of HO‐1 slows the progression of hypertension and proteinuria in SHR. These changes were associated with reduced renal oxidative stress and inflammation and increased indices of nitric oxide.
Upregulated TRPC3 expression and function in vascular smooth muscle during hypertension
Authors: Noorani Muzamil M.Z. , Chen Jie , Marrelli Sean P.
Published: June 2021

TRPC3 has been demonstrated to play a role in regulating arterial tone through smooth muscle cell (SMC) depolarization. Recent studies indicate that TRPC3 expression is upregulated in pulmonary artery SMC in idiopathic pulmonary hypertension. We sought to determine if TRPC3 was upregulated in the systemic circulation during hypertension, and if so, whether this upregulation renders arteries more contractile to physiological agonists.

Protein was extracted from carotid arteries (CA) of male SHR and WKY rats. Western blot analysis demonstrated 3.1 ± 1.2 times greater TRPC3 expression in SHR versus WKY. Next, TRPC3 function was evaluated in freshly isolated CA SMC by whole cell patch clamp; TRPC3 currents were elicited by extracellular application of uridine triphosphate (UTP; 60 µM). UTP‐stimulated currents were greater in SHR compared with WKY or previous studies with normotensive Long‐Evans rats. Peak UTP‐stimulated inward currents (at ‐110 mV) were ‐36, ‐18, and ‐23 pA, respectively.

In summary, we have demonstrated upregulated TRPC3 expression and function in CA during hypertension. Future planned studies will evaluate CA responses to contractile agonists. Supported by: AHA 0665100Y and NIH HL088435 (SPM)
Obligatory role for phosphatidylinositol 4, 5‐bisphosphate (PIP2) in activating native TRPC store‐operated channels (SOCs) in vascular myocytes
Authors: Saleh Sohag , Ju Min , Albert Anthony , Large William
Published: June 2021

We have previously shown that protein kinase C (PKC) has a pivotal role in activating diverse TRPC SOCs in vascular myocytes (Albert & Large, 2002; Saleh et al, 2008). The present work investigated mechanisms involved in linking PKC activity with gating of SOCs and provides evidence that PIP2 is an obligatory molecule in this process.

Bath application of PIP2 to quiescent inside‐out patches from rabbit portal vein myocytes activated SOC activity, which was inhibited by anti‐TRPC1 antibodies (Albert & Large, 2003; Saleh et al, 2008). Cyclopiazonic acid (CPA)‐, BAPTA‐AM‐ and phorbol esters (PDBu)‐induced SOC activity was inhibited by an anti‐PIP2 antibody and by pre‐treatment with agents that deplete tissue PIP2 levels. Pre‐treatment with PDBu and the PKC inhibitor, chelerythrine, enhanced and decreased SOC stimulation by PIP2. Co‐immunoprecipiation experiments showed association between PIP2 and TRPC1 at rest and moreover that PKC‐dependent phosphorylation of TRPC1 was increased by CPA and PDBu and decreased by chelerythrine.

These data clearly indicate that PIP2 activates SOCs and that PIP2 is obligatory for stimulation of SOCs via PKC‐dependent phosphorylation of TRPC1.

Albert & Large (2002) J Physiol 544 113‐25; Saleh et al (2008) J Physiol 566 2463‐76
SKA‐31, a new activator of KCa2 and KCa3.1 K+ channels, potentiates the EDHF response and lowers blood pressure
Authors: Wulff Heike , Sankaranarayanan Ananthakrishnan , Raman Girija , Busch Christopher , Schultz Tim , Zimin Pavel I. , Hoyer Joachim , Köhler Ralf
Published: June 2021

Small‐conductance (KCa2.1‐2.3) and intermediate‐conductance (KCa3.1) Ca2+‐activated K+ channels are critically involved in modulating Ca2+‐signaling and membrane potential in excitable and non‐excitable cells. Activators of these channels constitute useful pharmacological tools as well as potential new drugs for the treatment of ataxia, epilepsy, and hypertension. We here used the neuroprotectant riluzole as a template for the design of KCa2/3 channel activators that are potent enough for in vivo studies. Out of a library of 55 benzothiazoles we identified SKA‐31 (naphtho[1,2‐d]thiazol‐2‐amine), which activated KCa2.1‐2.3 channels with EC50s of 2‐3 μM and KCa3.1 with an EC50s of 250 nM. SKA‐31 exhibited improved selectivity over Na+ and Ca2+ channels and good PK properties (half‐life 12 h; plasma protein binding 40%). SKA‐31 potentiated EDHF‐mediated dilations of carotid arteries from KCa3.1+/+ mice but not from KCa3.1−/− mice. Administration of 10 and 30 mg/kg SKA‐31 lowered mean arterial blood pressure by 4 and 6 mmHg in normotensive mice and by 12 mmHg in angiotensin‐II‐induced hypertension. These effects were absent in KCa3.1‐deficient mice. With SKA‐31 we have designed a new pharmacological tool to study the role of KCa2/3 channel activation in vivo. The blood pressure lowering effect of SKA‐31 suggests KCa3.1 channel activation as a new therapeutic principle for the treatment of hypertension.
Enhanced vascular relaxation through epoxygenase depends on ATP‐sensitive K+ channels via adenosine A2A receptor: Role of high salt diet
Authors: Nayeem Mohammed A , Boegehold Matthew A , Ponnoth Dovenia S , Roush Kevin P , Zeldin Darryl C , Falck John R , Mustafa S. Jamal
Published: June 2021

We hypothesize that high salt (HS) diet promotes aortic relaxation in mice through epoxygenases activating ATP‐sensitive K+ channels, via adenosine A2A receptor (A2AAR). Aortae from male mice fed HS (4% NaCl) or normal salt (NS, 0.45% NaCl) diets for 4‐5 wks were used. Concentration responses to NECA (10−11‐10−5 M; non‐selective adenosine agonist) and CGS 21680 (A2A AR agonist, 10−12‐10−6 M) were obtained with inhibitors. NECA (10−6 M) and CGS 21680 (10−6 M) produced significant relaxation (p<0.05) in HS (NECA: 28.37 ± 3.96%; CGS 21680: 27.89 ± 4.55%) compared to NS (NECA: 4.09 ± 2.33%, CGS 21680: 4.92 ± 2.25%). MS‐PPOH (CYP epoxygenases inhibitor; 10−5M) & 14,15‐EEZE (14,15‐EET blocker, 10−5M) abolished CGS 21680 induced relaxation (p<0.05) while glibenclamide (KATP channel blocker; 10−5M) & 5‐hydroxydecanoate (mitochondrial KATP channel blocker; 10−5M) changed into contraction (p<0.05) in HS. DDMS (CYP4A inhibitor; 10−5M) & HET0016 (20‐HETE blocker; 10−5M) have increased relaxation (p<0.05) in NS. However, no significant difference was found between DDMS & HET0016 treated HS & NS vs. control HS aorta. CYP2J2 (46%) and CYP4A (35%) proteins were up (p<0.05) in HS and NS respectively. These data suggest that HS diet possibly enhanced CYP2J2 activity causing increased opening of KATP channels leading to higher aortic relaxation through A2A AR. Supported by HL027339, HL094447, AHA0755264B, GM 31278 & IRP NIEHS /NIH
Cardiovascular effects of noradrenaline injected into the Medial Nucleus of Amígdala (MeA) of unanesthetized rats.
Authors: Fortaleza Eduardo Trindade , Scopinho América Augusto , Correa Fernando Morgan Aguiar
Published: June 2021

Introduction

The MeA, is involved with physiological and behavioral processes modulation, as well as regulation of the autonomic nervous system. Some evidences indicating that electrical rats MeA stimulation is able to evoke cardiovascular response. The noradrenaline (NA) is a neurotransmitter involved in the control of cardiovascular responses into the several structures in the central nervous system. The MeA received noradrenergic innervations of the A6 neurons and locus coeruleus (LC). Moreover, binding studies demonstrate noradrenergic receptors in this area.

Objective

The aim of the present work is characterize the cardiovascular responses evoked by local administration of NA in the MeA.

Methods and Results

Male Wistar rats were used. Cannulaes was implanted in the MeA using a stereotaxic apparatus. A catheter was implanted into the femoral artery for blood pressure and heart rate (HR) recording. Injecting different doses of NA (3, 9, 27 or 45 nmol/100 nL) into the MeA of normotensive rats (baseline MAP=100±2 mmHg and HR=369 ± 4bpm, n=25) caused dose‐related pressor responses and HR decrease. Nonlinear regression analysis indicated a significant correlation between doses and cardiovascular responses.

Conclusion

Our results reinforce the idea that noradrenergic mechanisms into the MeA are involved in cardiovascular control.

Financial Supports

FAPESP, CNPQ and FAEPA.
Reverse Respiratory Sinus Arrhythmia and Baroreceptor Sensitivity in Amyotropic lateral Sclerosis
Authors: Bartels Matthew N , De Meersman Ronald E , Atkeson Amy , Downey John A , Basner Robert C
Published: June 2021

Respiratory sinus arrhythmia (RSA) is heart rate variability in synchrony with normal respiration, by which the R‐R interval on an electrocardiogram (EKG) is shortened during inspiration and prolonged during expiration. During a normal respiratory cycle intrathoracic pressure (ITP) decreases and increases during inhalation and exhalation, respectively. These pressure changes stimulate baroreceptors (BRS).

AIMS

We studied baroreceptor responses during continuous positive airway pressure (CPAP), in which ITPs are reversed compared to normal breathing. In addition, we compared the BRS responses during CPAP between amyotropic lateral sclerosis patients (ALS) and normal subjects.

Methods

Respiration, EKG, and beat‐to‐beat blood pressures were collected during CPAP and sham treatments. Baroreceptor analysis was derived using the transfer function between blood pressure and R‐R interval changes. Analysis of variance was used to determine statistical differences at an a‐level of P < .05.

Results

Preliminary trends in BRS were seen between the groups (ALS < 3±.02 mmHg/sec vs normals > 6±2.2 mmHg/sec).

Discussion

Preliminary results suggest that BRS is maintained during CPAP but appears to trend toward differences in magnitude between ALS patients and normals. VIDDA foundation.
Hypothalamic paraventricular nucleus non‐NMDA receptors mediate the pressor response to noradrenaline microinjected into the bed nucleus of the stria terminalis of unanesthetized rats.
Authors: Crestani Carlos Cesar , Tavares Rodrigo F. , Busnardo Cristiane , Alves Fernando H.F. , Correa Fernando M.A.
Published: June 2021

Noradrenaline microinjected into the bed nucleus of the stria terminalis (BST) evoke pressor response, which is mediated by acute systemic vasopressin release. Hypothalamic paraventricular nucleus (PVN), but not the supraoptic nucleus, mediates this pressor response. Thus, the aim of the present work was to evaluate the involvement of PVN‐glutamatergic neurotransmission on the pressor response to noradrenaline microinjected into the BST of unanesthetized rat. For this, male Wistar rats had guide cannulas implanted in the BST and ipsilaterally in the PVN. Catheters was implanted in the femoral artery for mean arterial pressure (MAP) and heart rate (HR) recording. PVN pretreatment with the selective NMDA glutamatergic receptor antagonist LY235959 did not affect the pressor (30±4 vs 31±2 mmHg; p>0.05) and bradycardiac (‐35±6 vs‐37±2 bpm; p>0.05) responses to noradrenaline microinjected into the BST. However, when the selective non‐NMDA glutamatergic receptor antagonist NBQX was microinjected into the PVN the pressor (31±3 vs 8±2 mmHg; p<0.001) and bradycardiac (‐36±5 vs ‐8±1 bpm; p<0.003) responses were significantly reduced. Thus, our results suggest that PVN non‐NMDA receptors mediate the pressor response to noradrenaline microinjected into the BST.
Absence of salt sensitivity in iNOS knockout mice
Authors: Van Vliet Bruce N , Ryan Suzanne C , McGuire John J
Published: June 2021

The ability of aminoguanidine to promote salt‐sensitive hypertension has led to the suggestion that the inducible form of nitric oxide synthase (iNOS, NOS‐2) contributes importantly to the regulation of salt balance and blood pressure (BP). Here, we tested the hypothesis that iNOS knockout mice (iNOS‐/‐) have increased salt sensitivity of BP relative to control animals (iNOS+/+). Male mice of either strain were placed on regular (0.5% NaCl, RS) or high (8% NaCl, HS) salt diet at 9 wks, and 24h diastolic (DBP) and systolic (SBP) BP were assessed by telemetry after 3 months. In iNOS+/+ mice, 3 months of HS was associated with a modest elevation of BP compared to the RS group (RS vs HS: DAP, 91 ± 4 vs 98 ± 6 mmHg, P<0.05, SAP, 124 ± 2 vs 128 ± 5 mmHg, NS), consistent with previous studies. In contrast, there was no evidence of this effect of HS in iNOS‐/‐ mice (RS vs HS: DAP: 95 ± 4 vs 92 ± 2 mmHg, NS, SAP: 126 ± 4 vs 124 ± 6 mmHg, NS). The BP of iNOS‐/‐ and iNOS+/+ mice on RS diet were not significantly different. The BP response to brief (4 day) increases (RS to HS) or decreases (HS to RS) in salt intake did not differ between the two strains. In summary, our results demonstrate that iNOS knockout mice are normotensive and do not exhibit an exaggerated BP response to high salt. We reject our original hypothesis and conclude that absence of iNOS does not lead to an obligatory increase of salt sensitivity or BP. Supported by the Canadian Institutes of Health Research.
Sex differences in the balance of sympathetic activity, peripheral resistance and cardiac output: implications for blood pressure control
Authors: Hart Emma C , Charkoudian Nisha , Joyner Michael J , Curry Timothy B , Eisenach John H , Wallin Gunnar
Published: June 2021

The sensitivity of the baroreflex control of muscle sympathetic nerve activity (MSNA) represents the responsiveness of MSNA to changes in blood pressure, whereas the baroreflex threshold diagram evaluates the likelihood of a burst occurrence over a range of resting blood pressure values. We hypothesized that the slope of the threshold diagram would show a significant positive correlation with sympathetic baroreflex sensitivity (BRS). We compared BRS calculated by the Modified Oxford technique (ModOx) with the slope and midpoint (T50) values from threshold analysis (threshold) in 10 participants (9M, age 26 yrs ± 3[mean ± SEM]). MSNA (peroneal microneurography) and blood pressure (brachial catheter) were measured at rest and during vasoactive drug boluses (ModOx). A threshold diagram was created for each subject during rest by associating DBP to the % occurrence of a burst over a 4 min period prior to the ModOx drugs. The midpoint (T50) of this diagram was defined as the DBP at which 50% of the diastoles were associated with a burst. ModOx‐derived BRS positively correlated with the slope of the threshold diagram (r = 0.64, P<0.05), but not with the T50 (r =0.11, P > 0.2). Our results suggest that the slope of the threshold diagram may be a better index of ModOx‐derived BRS values compared to more commonly used "spontaneous" baroreflex techniques.

NIH HL‐083947
Age dependent effects of haemorrhage on the arterial baroreflex control of heart rate in conscious lambs
Authors: Samhan Mohamed A , Qi Wei , Smith Francine G
Published: June 2021

Previously, we showed that arterial pressure decreased after moderate haemorrhage in conscious lambs, whereas a compensatory increase in heart rate occurred only in newborns. These findings provided evidence to suggest an age‐dependent effect of haemorrhage on the arterial baroreflex control of heart rate. Therefore, in the present study, the arterial baroreflex was assessed in conscious lambs aged 14±1 days (G I, N=4) and 43±7 days (G II, N=6) before (control, C) and at 30 and 60 min after haemorrhage (30% of calculated blood volume). The following parameters governing the arterial baroreflex were evaluated: Heart rate range (P1), slope coefficient (P2), systolic arterial pressure at midpoint (P3), minimum HR (P4), and maximum gain (Gmax). Values are mean±SEM; *p<0.05 compared with C; †p<0.05 compared with G I.

Predominant effects of haemorrhage were: a decrease in P1 which was greater in G I than G II, and a decrease in Gmax which was greater in G II than G I. Therefore, severe haemorrhage alters several parameters governing the arterial baroreflex control of heart rate, these effects being developmentally regulated.

This research was supported by the Canadian Institutes of Health Research (CIHR).
Effects of aging, hypertension, and diabetes on low‐frequency arterial pressure oscillations
Authors: Kiviniemi Antti M , Tulppo Mikko P , Seppänen Tapio , Norton Katelyn , Frances Maria F , Nolan Robert P , Huikuri Heikki V , Shoemaker Kevin
Published: June 2021

Low‐frequency (LF, 0.04‐0.15 Hz) oscillations of arterial pressure are associated to sympathetic activity. We measured beat‐to‐beat systolic blood pressure (SBP) and respiration for YOUNG (n=39, 34±3 yrs) and OLD (n=40, 64±6 yrs) healthy subjects and patients with hypertension (HT, n=38, 60±7 yrs), coronary artery disease (CAD, n=16, 61±4 yrs) and diabetes (CAD+DM, n=29, 60±6 yrs) at supine rest. Spectral power (LFSBPpower) and center frequency (LFSBPf) of SBP oscillations within LF band were calculated. Adaptive filtering was applied to reduce the effects of slow breaths on SBP oscillations at LF. Significant group‐effects were found in LFSBPpower (YOUNG: 4.0±2.5, OLD 6.1±3.4, HT: 5.2±3.3, CAD: 4.2±2.6 and CAD+DM: 4.1±3.0 mmHg2, p=0.014) and LFSBPf (YOUNG: 0.073±0.015, OLD: 0.064±0.011, HT: 0.068±0.011, CAD: 0.054±0.007 and CAD+DM: 0.056±0.010 Hz, p<0.001). OLD had higher LFSBPpower (p=0.003) and lower LFSBPf (p=0.008) than YOUNG. LFSBPpower and LFSBPf did not differ between OLD and HT, whereas CAD had lower LFSBPf (p<0.001) and tended to have lower LFSBPpower (p=0.050) than OLD. No differences were found in LFSBPpower and LFSBPf between CAD and CAD+DM. We concluded that LF arterial pressure oscillations at resting condition are affected by age and cardiac disease but appear to be unaffected by diabetes in cardiac patients or by hypertension. Supported by Academy of Finland, TEKES Finland and CIHR.