Biomedical subjects

L Edvinsson

Publications and source records attributed to L Edvinsson.

At least 73 records · Page 4Linked to original sources

PubMed2000

Vasodilation in human subcutaneous arteries induced by neuropeptide Y is mediated by neuropeptide Y Y1 receptors and is nitric oxide dependent.

Neuropeptide Y (NPY) is known as a potent vasoconstrictor of peripheral blood vessels both in vivo and in vitro. There have been reports suggesting that NPY also has a dilatory effect. The aim of the present study was to elucidate whether NPY dilates small human subcutaneous arteries. Subcutaneous arteries, obtained from patients undergoing abdominal surgery, were mounted in in vitro tissue baths, and the vascular responses to NPY were investigated. The presence of mRNA encoding the human NPY Y1 receptor in endothelial cells from human umbilical veins was studied by the use of reverse transcriptase - polymerase chain reaction (RT-PCR). In arteries precontracted with the prostaglandin analogue U46619, NPY induced a concentration-dependent vasodilation (Emax 30 +/- 10% of the U46619-induced contraction), which was significantly inhibited by the NPY Y1 receptor antagonist BIBP3226 (1 microM), causing a rightward shift of the concentration-response curve, pEC50 7.1 +/- 0.3 vs. 7.7 +/- 0.3 for NPY alone. After pretreatment with the nitric oxide synthetase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (10 microM), the dilation was abolished (Emax 6 +/- 5% of the U46619-induced contraction). mRNA encoding the human NPY Y1 receptor was detected in endothelial cells from human umbilical veins. It was concluded that NPY induces vasodilation in human subcutaneous arteries. The dilation is mediated via the NPY Y1 receptor and is dependent on nitric oxide.

Arginine↗

PubMed2000

Neuropeptide Y stimulates DNA synthesis in human vascular smooth muscle cells through neuropeptide Y Y1 receptors.

We investigated the mitogenic effect, measured as [3H]thymidine incorporation, of neuropeptide Y (NPY) on smooth muscle cells (SMCs) from human subcutaneous arteries (diameter: 0.4 mm). NPY stimulated DNA synthesis in a concentration-dependent manner, Emax 32 +/- 5% relative to control. The effect was potently antagonised by the NPY Y1 receptor antagonist BIBP3226 ((R)-N2-(diphenylacetyl)-N-[(4-hydroxy-phenyl)methyl]-D-arginine-a mide), indicating the effect to be mediated via the NPY Y1 receptor. Noradrenaline (NA) also induced mitogenesis, Emax 35 +/- 10% relative to control. When added together, NPY and NA potentiated the [3H]thymidine incorporation, Emax 109 +/- 38% relative to control. Also, this effect seems to be mediated by the NPY Y1 receptor, since BIBP3226 blocked the effect (44 +/- 9% relative to control). The mitogenic effect of NPY and NA, two important transmitters of the sympathetic nervous system, might have clinical consequences on conditions with elevated sympathetic nerve activity.

Cells, Cultured↗

PubMed2000

Characterization of contractile P2 receptors in human coronary arteries by use of the stable pyrimidines uridine 5'-O-thiodiphosphate and uridine 5'-O-3-thiotriphosphate.

The present study was designed to evaluate the relative contribution of the different contractile P2 receptors in endothelium-denuded human coronary arteries by use of extracellular nucleotides, including the stable pyrimidines uridine 5'-O-3-thiotriphosphate (UTPgammaS) and uridine 5'-O-thiodiphosphate (UDPbetaS). The isometric tension of isolated vessel segments was recorded in vitro, and P2 receptor mRNA expression was examined by reverse transcription-polymerase chain reaction. alphabeta-Methylene-adenosine triphosphate (alphabeta-MeATP) elicited contractions at a low concentration (pEC(50) = 5.2), indicating the presence of contractile P2X receptors. The P2Y responses were analyzed after P2X receptor desensitization with 10 microM alphabeta-MeATP. The stable nucleotides UTPgammaS and adenosine 5'-O-3-thiotriphosphate (ATPgammaS), which are agonists of P2Y(2) or P2Y(4) receptors, were approximately 2 log units more potent than the endogenous UTP and ATP (pEC(50) = 4.6 and 3.8 for UTPgammaS and ATPgammaS). The efficacy of these responses were approximately double that of the P2X agonist alphabeta-MeATP (E(max) = 125% for UTPgammaS, 126% for ATPgammaS, and 68% for alphabeta-MeATP), suggesting a primary role for contractile P2Y(2/4) receptors. The P2Y(2) receptor agonist diadenosine tetraphosphate also stimulated contraction, whereas the selective P2Y(1) agonist adenosine 5'-O-thiodiphosphate and the selective P2Y(6) agonist UDPbetaS had no effect. Reverse transcription-polymerase chain reaction analysis of mRNA from endothelium-denuded human coronary arteries demonstrated strong bands for P2Y(2) and P2X(1), although bands for P2Y(1), P2Y(4), and P2Y(6) receptor mRNA could also be detected. In conclusion, the stable pyrimidines UDPbetaS and UTPgammaS are important tools for P2 receptor subtype characterization in intact tissues with ectonucleotidase activity. Extracellular nucleotides elicit contraction of human coronary arteries primarily by activation of P2Y(2) and P2X receptors, whereas a role for P2Y(1) and P2Y(6) receptors can be excluded. Antagonists of P2Y(2) and P2X receptors may be useful in the treatment of coronary vasospastic disorders.

Adenosine Triphosphate↗

PubMed2000

A pathophysiological view of primary headaches.

The cerebral circulation is innervated by sympathetic, parasympathetic and sensory nerves which store a considerable number of neurotransmitters. The role of these has been evaluated in primary headaches. A clear association between head pain and the release of calcitonin gene-related peptide (CGRP) was demonstrated. In cluster headache and in a case of chronic paroxysmal headache there was in addition release of vasoactive intestinal peptide (VIP) which was associated with facial symptoms (nasal congestion, rhinorrhea). In parallel with sumatriptan treatment head pain subsided and neuropeptide release normalised. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches.

Animals↗

PubMed1999

Positive inotropy of calcitonin gene-related peptide and amylin on porcine isolated myocardium.

Isolated porcine myocardial trabeculae from right atria and left ventricles were paced at 1.5 Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. Alpha calcitonin gene-related peptide (alpha-CGRP) increased contractile force in nearly half of the trabeculae, whereas the selective CGRP(2) receptor agonist [Cys(acetylmethoxy)(2,7)]-CGRP had effect in only a few. Preincubation with the CGRP(1) receptor antagonist alpha-CGRP-(8-37) (10(-6) M) almost completely blocked positive inotropic responses to alpha-CGRP. Amylin had weak positive inotropic effects in some atrial, but not in ventricular trabeculae. Adrenomedullin did not affect contractility in either atrial or ventricular trabeculae. In conclusion, these results suggest that alpha-CGRP has a positive inotropic effect that can be mediated by both CGRP(1) and CGRP(2) receptors. Amylin seems to have a potential positive inotropic effect on atrial tissue, whereas no direct effect of adrenomedullin could be measured.

Amyloid↗

PubMed1999

[Vasoactive transmitters in the coronary circulation].

Coronary resistance can be modified by perivascular, endothelial and humoral vasoactive substances. A network of perivascular nerve fibres is present in the adventitia and at the adventitial-medial border of human coronary arteries and veins, and immunocytochemical studies have provided evidence that several neuropeptides are localized in subpopulations of afferent and efferent nerve fibres supplying the human coronary vasculature. Neuropeptide Y seems to be co-localized with noradrenaline in adrenergic perivascular nerve fibres and vasoactive intestinal peptide co-localized with acetylcholine in parasympathetic nerves, whereas sensory perivascular nerves contain immunoreactivity to substance P and calcitonin gene-related peptide. On the other hand, nitric oxide and endothelin are synthesized in coronary endothelial cells. Humoral substances like gonadal hormones are also likely candidates in the regulation of coronary resistance. The presence of different vasoactive substances in the coronary vasculature and the potential of these substances to affect coronary vessel tone, suggest that they have an important role in the regulation of coronary blood flow.

Coronary Circulation↗

PubMed1999

Cytokines increase endothelin ETB receptor contractile activity in rat cerebral artery.

The plasticity of endothelin ETB receptor activity and the influence of pro-inflammatory cytokines was examined in cerebral artery. In fresh rat basilar artery, the selective ETB receptor agonist, sarafotoxin S6c, induced negligible contractions. However, after 1 day of organ culture, fully defined concentration-response curves were obtained in artery segments exposed to sarafotoxin S6c. Organ culture in the presence of either interleukin-1 beta or tumour necrosis factor-alpha, but not interleukin-2 or interleukin-6, further amplified the maximal contraction to sarafotoxin S6c. The plasticity of ETB receptor expression in cerebral arteries and sensitivity for pro-inflammatory cytokines, suggest a role in inflammatory cerebral diseases such as stroke.

Animals↗

PubMed1999

Cytokines induce increased endothelin ET(B) receptor-mediated contraction.

The effect of cytokines on the induction of contractile endothelin ET(B) receptors during organ culture was examined. Ring segments of rat superior mesenteric artery were used fresh or incubated for 24 h in Dulbecco's modified Eagle's medium alone, or with either interleukin-1beta, tumor necrosis factor-alpha (TNF-alpha) or interleukin-2. In fresh arterial segments there was no endothelin ET(B) receptor-induced contraction. After incubation, the selective endothelin ET(B) receptor agonist sarafotoxin 6c evoked a contraction of 22 +/- 6% relative to that induced by 60 mM K+. The endothelin ET(B) receptor-induced contraction was further increased to 125 +/- 25% and 157 +/- 29% by interleukin-1beta and TNF-alpha, respectively, while interleukin-2 did not alter the endothelin ET(B) receptor-induced contraction. The identity of the contractile receptor was confirmed as the endothelin ET(B) receptor by the use of an additional specific endothelin ET(B) receptor agonist, IRL 1620, and by antagonist experiments with FR 139317 and IRL 2500. The endothelin-1-induced contraction was not altered by either of the cytokines. Reverse transcriptase-polymerase chain reaction revealed increased levels of endothelin ET(B) mRNA, relative to endothelin ET(A) mRNA following organ culture, suggesting that contractile endothelin ET(B) receptors appear via de novo transcription. None of the cytokines changed the ratio of endothelin ET(A) and endothelin ET(B) receptor mRNA, indicating that the further increased sarafotoxin 6c-induced contraction is mediated through an enhancement of intracellular signalling mechanisms.

Animals↗

PubMed1999

Interleukin-1beta potentiates endothelin ET(B) receptor-mediated contraction in cultured segments of human temporal artery.

Segments of human temporal artery were placed in organ culture for up to 4 days and examined for endothelin ET(B) receptor activity in the presence and absence of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) by in vitro pharmacology and reverse transcriptase-polymerase chain reaction (RT-PCR). The contractile effect of prostaglandin F2alpha (used as a reference), was not significantly altered by culture or IL-1beta. However, the selective ET(B) agonist sarafotoxin S6c induced no contraction in fresh arteries, but marked contraction after culture. Both maximal contraction and potency to sarafotoxin S6c were increased in segments incubated with IL-1beta . The contraction was sensitive to BQ 788 (ET(B) antagonist), but not FR 139317 (ET(A) antagonist). Actinomycin D abolished the contraction, whereas only the cytokine-induced increase in contraction was inhibited by cycloheximide. ET(A) and ET(B) receptor mRNAs were detected in all arteries; predominantly for the ET(A) receptor in fresh arteries, and for the ET(B) receptor after culture. However, there was no change in the ET(A)/ET(B) receptor mRNA ratio after treatment with IL-1beta. This suggests de novo synthesis of contractile ET(B) receptors after organ culture and that IL- 1beta may further stimulate translation of the mRNA to active receptors. The results raise the possibility that contractile ET(B) receptors may be implicated in disease states with inflammatory processes.

Cycloheximide↗

PubMed1999

Messenger molecules and receptor mRNA in the human trigeminal ganglion.

The presence and distribution of neuromessenger molecules and receptor mRNA in human trigeminal ganglion was studied with immunocytochemical, in situ hybridisation and RT-PCR techniques. Immunofluorescence staining revealed that calcitonin gene-related peptide (CGRP) immunoreactive (-ir) neurons occurred in high numbers, constituting 36-40% of all nerve cell bodies in the ganglion. Accordingly, in situ hybridisation demonstrated CGRP mRNA in a large portion of the trigeminal neurons. A small number of the nerve cell bodies showed substance P (SP)-ir, (18%), nitric oxide synthase (NOS)-ir (15%), and pituitary adenylate cyclase activating peptide (PACAP)-ir (20%). Double immunostaining revealed that only few CGRP-ir neurons also were NOS-ir (less than 5%). The C-terminal flanking peptide of neuropeptide Y, C-PON, was not visible in any of the nerve cell bodies studied. Agarose gel electrophoresis of the RT-PCR products from the ganglia demonstrated the presence of mRNA corresponding to CGRP1, NPY Y1 and Y2, and VIP1 receptors. These results suggest both sympathetic and parasympathetic influence on the activity in the trigeminal ganglion.

Aged↗

PubMed1999

MAPKK-dependent growth factor-induced upregulation of P2Y2 receptors in vascular smooth muscle cells.

The ATP- and UTP-sensitive P2Y2 receptor which mediates both contractile and mitogenic effects has recently been shown to be upregulated in the synthetic phenotype of the vascular smooth muscle cell (VSMC). Using a competitive RT-PCR we demonstrate that the P2Y2 receptor mRNA is increased by fetal calf serum and other growth factors in a MAPKK-dependent way. This was confirmed at the functional level by examining UTP-stimulated release of intracellular Ca2+. Furthermore, the P2Y2 receptor mRNA is positively autoregulated by ATP and the mRNA is rapidly degraded with only 26% remaining after 1 h in the presence of actinomycin D. Our results indicate growth factor regulation and rapid turnover of the P2Y2 receptor mRNA, which may be of importance in atherosclerosis and neointima formation after balloon angioplasty.

Animals↗

PubMed1999

Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques.

5-Hydroxytryptamine (5-HT) can produce both vasoconstrictor and vasorelaxant effects in human coronary arteries and the response to 5-HT can be influenced by the presence of disease. The aim of the present study was to elucidate the 5-HT receptor subtypes responsible for mediating 5-HT-evoked contraction of human coronary arteries using pharmacological, molecular and immunocytochemical approaches. Normal human coronary arteries, with intact endothelium, were mounted in tissue baths, and the vascular responses to 5-HT and 5-HT receptor agonists were studied. The effects of 5-HT1 and 5-HT2 receptor antagonists on these responses were also studied. Expression of messenger ribonucleic acid (mRNA) encoding different 5-HT receptors in human coronary arteries, atrium, ventricle wall and epicardium was determined using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. The expression of 5-HT1B or 5-HT1D receptor protein was studied using subtype selective antibodies and standard immunocytochemical techniques. The rank order of 5-HT receptor agonist potency in causing vasoconstriction was 5-carboxamido tryptamine, (5-CT) > zolmitriptan = BW183C91 (N10-desmethyl zolmitriptan) = alpha-methyl-5-hydroxytryptamine (alpha-CH3-5-HT) = 5-HT = sumatriptan > 2-methyl-5-hydroxytryptamine (2-CH3-5-HT) = 8-hydroxy-DPAT (8-OH-DPAT). Alpha-CH3-5-HT, 5-CT, 5-HT, zolmitriptan and BW 183C91 were significantly more potent (approximately 3-fold) than sumatriptan and 2-CH3-5-HT, which in turn were more potent than 8-OH-DPAT. Ketanserin and methiothepin (5-HT2 and 5-HT1 receptor antagonists, respectively) caused parallel rightward shifts of the concentration-effect curves to alpha-CH3-5-HT or 5-CT, respectively, without changing the maximum contractile response. In human coronary arteries, atrium. ventricle and epicardium. RT-PCR products corresponding to the human 5-HT2A, 5-HT1B and 5-HT1F receptors were expressed in high levels, mRNAs coding for 5-HT7, 5-HT1A and 5-HT1D receptors were only weakly expressed. No 5-HT1F receptor mRNA was detected. In coronary arteries there was a differential expression of 5-HT1B versus 5-HT1D receptor mRNAs, with 5-HT1B mRNAs being found in greater abundance. Dense 5-HT1B-immunoreactivity was detected on smooth muscle layer within coronary artery, however, 5-HT1D-immunoreactivity was not detected. It is concluded that 5-HT-evoked contraction of human coronary arteries is most probably mediated via the activation of both 5-HT1B and 5-HT2A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1999

Neuronal messengers and peptide receptors in the human sphenopalatine and otic ganglia.

A majority of the parasympathetic nerve fibers to cranial structures derive from the sphenopalatine and otic ganglia. In particular, blood vessels are invested with a rich supply of dilator fibers of parasympathetic origin. In the present study, we have examined the occurrence of noncholinergic neuromessengers and neuropeptide receptors in the human sphenopalatine and otic ganglia. Vasoactive intestinal peptide (VIP)-immunoreactive (ir) nerve cell bodies occurred in high numbers in the sphenopalatine and otic ganglia. Likewise, high numbers of NOS- and PACAP-containing nerve cell bodies were seen in both ganglia. Autofluorescent lipofuscin, characteristic of adult human nervous tissue, was present within many nerve cell bodies in both ganglia. Receptor mRNA was studied with reverse transcriptase-polymerase chain reaction (RT-PCR). Total RNA from the sphenopalatine and otic ganglia was successfully extracted. By using appropriate sense and antisense primers, oligonucleotides were designed from the human sequences derived from GenBank, corresponding to human NPY Y1, CGRP1 and VIP1 receptors. In the sphenopalatine ganglion, we revealed the presence of mRNA for the human NPY Y1 and VIP1 receptors but not the CGRP1 receptor. The otic ganglion was found to react positively only for primers to mRNA for VIP1 but not for CGRP1 or NPY Y1 receptors.

Aged↗

PubMed1999

The human superior cervical ganglion: neuropeptides and peptide receptors.

Noradrenaline (NA)- and neuropeptide Y (NPY)-containing cell bodies were found to occur in high numbers (>75% of all cells were positive) in the human superior cervical ganglion and distributed homogeneously throughout the ganglion and showed colocalisation. A few cell bodies were VIP-immunoreactive (-ir) (less than 5%) but none of them showed NOS-, CGRP- or SP-ir. Receptor mRNA expression was studied with RT-PCR. Total RNA from the superior cervical ganglion was successfully extracted. By using appropriate sense and antisense oligonucleotides designed from the published human sequences, we could show the presence of mRNA for the human NPY Y1, NPY Y2 and VPAC1 receptors but not CGRP1 receptor mRNA.

Aged↗

PubMed1999

Relaxing effect of insulin in renal arteries from diabetic rats.

Abnormal renal vasomotor tone exists in the early stages of diabetes mellitus. Insulin has been proposed to modulate renal function and to possess vasodilatory effects. The present study was initiated in order to evaluate the direct effect of insulin on isolated renal arteries. Twelve insulin-treated streptozotocine diabetic rats with diabetes for 50 days were compared with 15 weight-matched control rats. The contractile responses to 60 mM K+ and 10(-4) M noradrenaline, and the insulin- (0.8-6.4 I.U./ml) induced relaxation of vessels precontracted with noradrenaline, were similar in diabetic and control rats. There was a tendency towards greater relaxation in diabetic (71%) than in control rats (54%). Nw-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) given before noradrenaline tended to attenuate the insulin-induced relaxation, while addition of L-arginine (10(-6) M) to L-NAME attenuated the relaxation in diabetic but increased it in control rats (P < 0.05). The effect of insulin was tested further in control rats and was not influenced by administration of a single dose (10(-6) M) of indomethacin or propranolol given instead of L-NAME. The effect of a single dose of methylene-blue, given before noradrenaline, was tested in control rats in varying doses between 2 x 10(-6) and 2 x 10(-4) M. In the highest concentration it made no difference whether insulin was given or not and there was a similar relaxing effect in diabetic and control arteries. In conclusion, the present study showed that insulin per se has a relaxing effect on renal arteries. There was a tendency to greater relaxation in diabetic than in control rats, an effect which was attenuated by in-vitro-pretreatment with L-NAME as well as with L-NAME and L-arginine in diabetic vessels, while relaxation was increased in control vessels. This may indicate that the effect of insulin may be mediated through nitric oxide in diabetic but not in control rats. The effects of insulin in control vessels were not modified in vitro by indomethacin, propranolol or methylene-blue.

Animals↗

PubMed1999

Altered ratio of endothelin ET(A)- and ET(B) receptor mRNA in bronchial biopsies from patients with asthma and chronic airway obstruction.

Using a reverse transcription-polymerase chain reaction (RT-PCR) based assay the ratio of mRNA for the human endothelin ET(A) and ET(B) receptors in bronchial biopsies was assessed. In patients with diagnoses like bronchial cancer, endothelin ET(A) mRNA was the dominating subtype (ratio 3.74 +/- 0.99). Subjects with the diagnosis of asthma or chronic obstructive pulmonary disease showed significantly higher levels (ratio 0.81 +/- 0.04) of endothelin ET(B) receptor mRNA compared to endothelin ET(A) receptor mRNA. Our results indicate alterations in the endothelin receptor balance in these states.

Aged↗

PubMed1999

Expression of calcitonin gene-related peptide-1 receptor mRNA in human tooth pulp and trigeminal ganglion.

Numerous nerve fibres containing calcitonin gene-related peptide (CGRP) were found by immunocytochemistry in human molar pulp. These nerves were often seen around small blood vessels and as free endings without vascular contact. In the trigeminal ganglion a large number of CGRP-immunoreactive nerve-cell bodies, mostly of small to medium size, was encountered. Reverse transcriptase-polymerase chain reaction, using specific sense and antisense primers, detected mRNA expression of the human CGRP1 receptor in the pulp tissue and the trigeminal ganglion. Thus, both CGRP-containing nerve fibres and CGRP1 receptor mRNA are present in human tooth pulp, where they may be involved in the regulation of vascular tone and other local reactions to injury.

Adult↗

PubMed1999

Congestive heart failure induces downregulation of P2X1-receptors in resistance arteries.

OBJECTIVE: Congestive heart failure (CHF) is accompanied by enhanced peripheral sympathetic nerve activity, increased vascular resistance and impaired peripheral blood flow. Besides noradrenaline and neuropeptide Y, the sympathetic nervous system also releases ATP, which has contractile effects mediated by different subtypes of P2-receptors on the vascular smooth muscle cells. The present study was designed to examine postsynaptic changes of the contractile responses to ATP and other extracellular nucleotides in CHF. METHODS: CHF was induced by left coronary artery ligation resulting in a reproducible myocardial infarction in Sprague-Dawley rats. Contractile responses were examined in cylindrical segments of aorta and the mesenteric artery after endothelium removal. To determine if an altered response was regulated on the transcriptional level, competitive reverse transcription polymerase chain reaction (RT-PCR) was used to estimate the amount of P2X1-receptor mRNA. RESULTS: ATP, which is both a P2X1- and a P2Y-receptor agonist, induced a weaker contraction in the mesenteric artery from CHF as compared to sham operated rats. A decrease in both potency and maximum contraction was shown for the selective P2X1-receptor agonist, alpha beta-MeATP, in the mesenteric artery (pEC50 = 6.04 vs. 5.76, Cmax = 57% vs. 33%, sham vs. CHF operated rats), but not in the aorta. Competitive RT-PCR also revealed decreased P2X1-receptor mRNA levels in CHF operated rats in the mesenteric artery (9106 x 10(3) vs. 714 x 10(3) molecules/microgram, sham vs. CHF operated rats), while it remained unaltered in the aorta. To study the P2Y-receptor induced contractile effects, the P2X1-receptors were first desensitised with alpha beta-MeATP (10(-5) M for 8 min). After P2X1-receptors desensitisation, UTP and UDP induced strong contractions in both the mesenteric artery and in the aorta, while ATP and ADP were much less effective. These contractions were not altered by CHF, indicating that vascular contraction mediated by P2Y-receptors are unaffected by CHF. CONCLUSION: CHF induces downregulation of P2X1-receptor stimulated contraction in the mesenteric artery depending on decreased mRNA synthesis for the receptor, while the P2Y-receptor activity remains unchanged. Downregulation of P2X1-receptors appears to be specific for peripheral resistance arteries. This may represent a compensatory response to enhanced peripheral sympathetic nerve activity and increased vascular resistance in CHF.

Adenosine Diphosphate↗