Effect of celiprolol therapy on arterial dilatation in experimental hypertension

Tolvanen, Jari-Petteri; Wu, Xiumin; Kähönen, Mika; Sallinen, Kirsimarja; Mäkynen, Heikki; Pekki, Anu; Pörsti, Ilkka

doi:10.1111/j.1476-5381.1996.tb16015.x

Cited by 15 publications

(4 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23 Moreover, the present study has shown that celiprolol exerts beneficial effects in rats with endothelial dysfunction in the early phase of hypertension. Consistent with our results, long-term treatment with celiprolol, even at its subdepressor dose (5 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 PO), has been reported to restore endothelial dysfunction of mesenteric arteries of spontaneously hypertensive rats, 24 suggesting that the beneficial effects of celiprolol in hypertension are not only due to reduction in blood pressure. Therefore, stimulation of NO release caused by celiprolol may be a mechanism underlying its vascular action.…”

Section: Discussionsupporting

confidence: 79%

Effects of Vasodilatory β-Adrenoceptor Antagonists on Endothelium-Derived Nitric Oxide Release in Rat Kidney

et al. 1999

View full text Add to dashboard Cite

The mechanisms for the vascular actions of vasodilatory-blockers remain undetermined. For some kinds of-blockers, the involvement of nitric oxide (NO) has been suggested. We studied the effects of vasodilatory-blockers on renal perfusion pressure (RPP) and NO release in the rat kidney. Infusion of bopindolol, celiprolol, and nebivolol caused a dose-dependent reduction in RPP and an increase in NO release (RPP: bopindolol 10 6 mol/L, 232%; celiprolol 10 4 mol/L, 272%; nebivolol 10 5 mol/L, 353%; NO: bopindolol 10 6 mol/L, 332; celiprolol 10 4 mol/L, 412; nebivolol 10 5 mol/L, 455 fmol min 1 g kidney 1 , meanSEM). Metergoline (10 6 mol/L), a 5-hydroxytryptamine (5-HT) 1/2 antagonist, or NAN-190 (10 6 mol/L), a 5-HT 1A antagonist, almost completely abolished the vasorelaxation and NO release caused by bopindolol, celiprolol, and nebivolol. However, neither propranolol nor bisoprolol decreased RPP. Celiprolol and nebivolol caused vasodilation in the rat thoracic aorta, and it was markedly reduced by endothelial denudation, N-nitro-L-arginine methyl ester (10 4 mol/L), or NAN-190 (10 6 mol/L). In deoxycorticosterone acetate-salt hypertensive rats, 4-week administration of celiprolol (50 mg kg 1 d 1 IV) restored the responses regarding RPP and NO release to acetylcholine. These results suggest that several-blockers exert their vasodilatory action through the 5-HT 1A receptor/NO pathway and that treatment with these-blockers may protect against endothelial injury in hypertension. (Hypertension. 1999;33[part II]:467-471.) Key Words: nitric oxide kidney receptors, adrenergic, beta 5-hydroxytryptamine T he mechanism for vasodilation by some-adrenoceptor antagonists (-blockers) is not fully understood. It has been partly explained by intrinsic sympathomimetic activity (ISA). 1 Celiprolol 2 and dilevalol 3 are known to stimulate 2-adrenoceptors. Other mechanisms, such as the blockade of calcium channels by betaxolol 4 and the blockade of-adrenoceptors, have been reported, suggesting that the mechanisms for vasodilator-blockers may be heterogeneous. Although vasodilatory-blockers have little negative chronotropic actions, previous studies have shown that the long-term administration of bucindolol or carvedilol is beneficial in terms of ventricular function and mortality rate in congestive heart failure, 5,6 probably because of the reduction in cardiac afterload and the increase in coronary blood flow. Recent studies have also suggested that several sorts of vasodilatory-blockers, such as tertatolol and nebivolol, exert their effects partly via endothelium-derived nitric oxide (NO) release because their vasodilator effects are endothelium dependent and are suppressed by N-nitro-L-arginine, an NO synthase (NOS) inhibitor; by hemoglobin, a scavenger of NO; or by methylene blue, a soluble guanylate cyclase inhibitor. 7-10 If NO were involved in the effects of vasodilatory-blockers, we could expect these to exert nitrate-like effects and prevent cardiovascular complications, including ischemic organ damage. However, the mechanism...

show abstract

Section: Discussionsupporting

confidence: 79%

Effects of Vasodilatory β-Adrenoceptor Antagonists on Endothelium-Derived Nitric Oxide Release in Rat Kidney

et al. 1999

View full text Add to dashboard Cite

show abstract

“…In fact, some interventions have been effective in correcting ␤AR signaling in hypertension, such as dietary salt restriction 7 or pharmacological treatment. 11 Recently, a novel tool to modulate ␤AR signaling in a selective manner has been provided by adenoviral-mediated gene transfer of the human ␤ 2 AR cDNA. Indeed, in cardiac myocytes from both normal 12 and failing hearts, 13,14 adenoviral-mediated delivery and overexpression of the ␤ 2 AR enhanced signaling and physiological responses to ␤AR agonists.…”

mentioning

confidence: 99%

β ₂ -Adrenergic Receptor Gene Delivery to the Endothelium Corrects Impaired Adrenergic Vasorelaxation in Hypertension

et al. 2002

View full text Add to dashboard Cite

Background-Impaired ␤-adrenergic receptor (AR)-mediated vasorelaxation in hypertension plays a role in increased peripheral vascular resistance and blood pressure. Because the ␤ 2 AR is the most abundant vascular AR subtype, we sought to enhance ␤AR vasorelaxation by overexpressing ␤ 2 ARs via adenoviral-mediated gene transfer (AD␤ 2 AR) to the vascular endothelium of the carotid artery. Methods and Results-In normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, we exposed the right common carotid artery to AD␤ 2 AR in situ for 15 minutes by injection into the lumen while the blood flow was interrupted. Control carotids received an empty vector (ADempty). Three days later, transgene expression and selective endothelial localization were confirmed in infected vessels. Vasoregulation after ␤ 2 AR overexpression (2-fold) was studied in isolated organ baths. AD␤ 2 AR carotid responses to ␣ 1 AR and ␣ 2 AR agonists were not affected, whereas responses to epinephrine were altered and ␤AR-mediated vasorelaxation was enhanced after ␤ 2 AR overexpression. As expected, ␤AR-mediated vasodilatation in control carotids of SHR rats was significantly less than in similar control WKY carotid arteries. AD␤ 2 AR treatment enhanced ␤AR vasorelaxation in SHR to levels similar to those seen in AD␤ 2 AR WKY carotids. Conclusions-Our results demonstrate a critical role for the endothelium in ␤AR-mediated vasorelaxation and suggest that impaired ␤AR signaling may account for dysfunctional ␤AR vasorelaxation in hypertension rather than impaired endothelium-dependent nitric oxide metabolism.

show abstract

“…In some cases (e.g. relaxations to nitric oxide donor and contractions to NA) the magnitude of this variation exceeded the difference previously observed between corresponding sections of the superior mesenteric arteries from Wistar-Kyoto rats and spontaneously hypertensive rats (Kahonen et al 1995;Makynen et al 1995;Tolvanen et al 1996).…”

Section: Discussionmentioning

confidence: 79%

Variations of Arterial Responses in vitro in Different Sections of Rat Main Superior Mesenteric Artery

Tolvanen

Sallinen

et al. 1998

Pharmacology & Toxicology

Self Cite

View full text Add to dashboard Cite

Abstract;We examined the control of vascular tone in rat main superior mesenteric artery. Three standard rings (3 mm in length) of the mesenteric artery were cut, beginning 5 mm, 13 mm and 21 mm distally from the mesenteric arteryaorta junction. In noradrenaline-precontracted rings, relaxations to acetylcholine in the absence and presence of the cyclooxygenase inhibitor diclofenac, did not differ in the studied sections. However, the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, attenuated the diclofenac-resistant responses to acetylcholine more effectively in the proximal than the distal section. Glibenclamide, an inhibitor of ATP-sensitive K + channels, diminished relaxations evoked by acetylcholine only in the distal section, whereas the inhibitor of Ca2+ activated K+ channels, apamin, attenuated the responses in all sections. Furthermore, relaxation sensitivity to nitroprusside and isoprenaline was lower in the proximal than distal section. Arterial contractile sensitivity to noradrenaline and potassium chloride was higher, while the maximal contractile force generation was lower in the proximal than the distal part. In conclusion, in different sections of rat main superior mesenteric artery considerable variability was observed in vasoconstrictor and vasodilator responses, as well as in the contribution of endothelial nitric oxide and endothelium-mediated hyperpolarization to vasodilation. Therefore, the present results emphasize the fact that only corresponding vessel segments should be used when investigating the control of arterial tone.Numerous findings concerning arterial physiology and pathophysiology originate from studies performed on the superior mesenteric artery of the rat (Foster et al. 1992;Asano et al. 1993;Parsons et al. 1994). Previous investigations have revealed variations in arterial responses between the superior mesenteric arteries of different species, these arteries and other arteries of the same species, and between the conduit and the resistance part of the same superior mesenteric arteries (Nagao et al. 1992;Hwa et al. 1994;Kong et al. 1994;Roberts-Thomson et al. 1994). However, little is known about the homo-or heterogeneity of vascular tone in the conduit part of the superior mesenteric arteries. Therefore, the present experiments were designed to elucidate possible functional differences within the conduit part of this artery by examining vascular responses to contractile agents and to endothelium-independent anddependent vasodilators in different sections of the main superior mesenteric arteries of Wistar rats. Materials and MethodsAnimals and experimental design. Forty male Wistar rats were obtained from the experimental animal laboratory of University of Tampere. The animals were housed four to a cage in a standard experimental animal laboratory (illuminated 6 a.m.-6 pm., temperature 22'3, and had free access to drinking fluid (tap water) and Author for correspondence: Jari-Petteri Tolvanen, Department of Pharmacological Sciences, University of Tampere, P...

show abstract

Effect of celiprolol therapy on arterial dilatation in experimental hypertension

Cited by 15 publications

References 34 publications

Effects of Vasodilatory β-Adrenoceptor Antagonists on Endothelium-Derived Nitric Oxide Release in Rat Kidney

Effects of Vasodilatory β-Adrenoceptor Antagonists on Endothelium-Derived Nitric Oxide Release in Rat Kidney

β ₂ -Adrenergic Receptor Gene Delivery to the Endothelium Corrects Impaired Adrenergic Vasorelaxation in Hypertension

Variations of Arterial Responses in vitro in Different Sections of Rat Main Superior Mesenteric Artery

Contact Info

Product

Resources

About

Effect of celiprolol therapy on arterial dilatation in experimental hypertension

Cited by 15 publications

References 34 publications

Effects of Vasodilatory β-Adrenoceptor Antagonists on Endothelium-Derived Nitric Oxide Release in Rat Kidney

Effects of Vasodilatory β-Adrenoceptor Antagonists on Endothelium-Derived Nitric Oxide Release in Rat Kidney

β 2 -Adrenergic Receptor Gene Delivery to the Endothelium Corrects Impaired Adrenergic Vasorelaxation in Hypertension

Variations of Arterial Responses in vitro in Different Sections of Rat Main Superior Mesenteric Artery

Contact Info

Product

Resources

About

β ₂ -Adrenergic Receptor Gene Delivery to the Endothelium Corrects Impaired Adrenergic Vasorelaxation in Hypertension