Biomaterial Database

Mechanisms of vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34 in rat bone resistance arteries. 2016

T Benson, and T Menezes, and J Campbell, and A Bice, and B Hood, and R Prisby

Department of Kinesiology, University of Texas at Arlington, Arlington, TX, 76019, USA.

Parathyroid hormone (PTH) augments bone metabolism and bone mass when given intermittently. Enhanced blood flow is requisite to support high tissue metabolism. The bone arteries are responsive to all three PTH analogs, which may serve to augment skeletal blood flow during intermittent PTH administration. BACKGROUND PTH augments bone metabolism. Yet, mechanisms by which PTH regulates bone blood vessels are unknown. We deciphered (1) endothelium-dependent and endothelium-independent vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34, (2) the signaling pathways (i.e., endothelial nitric oxide synthase [eNOS], cyclooxygenase [COX], protein kinase C [PKC], and protein kinase A [PKA]), and (3) receptor activation. METHODS Femoral principal nutrient arteries (PNAs) were given cumulative doses (10(-13)-10(-8) M) of PTH 1-84, PTH 1-34, and PTHrP 1-34 with and without signaling pathway blockade. Vasodilation was also determined following endothelial cell removal (i.e., denudation), PTH 1 receptor (PTH1R) inhibition and to sodium nitroprusside (SNP; a nitric oxide [NO] donor). RESULTS Vasodilation was lowest to PTH 1-34, and maximal dilation was highest to PTHrP 1-34. Inhibition of eNOS reduced vasodilation to PTH 1-84 (-80 %), PTH 1-34 (-66 %), and PTHrP 1-34 (-48 %), evidencing the contribution of NO. Vasodilation following denudation was eliminated (PTH 1-84 and PTHrP 1-34) and impaired (PTH 1-34, 17 % of maximum), highlighting the importance of endothelial cells for PTH signaling. Denuded and intact PNAs responded similarly to SNP. Both PKA and PKC inhibition diminished vasodilation in all three analogs to varying degrees. PTH1R blockade reduced vasodilation to 1, 12, and 12 % to PTH 1-84, PTH 1-34, and PTHrP 1-34, respectively. CONCLUSIONS Vasodilation of femoral PNAs to the PTH analogs occurred via activation of the endothelial cell PTH1R for NO-mediated events. PTH 1-84 and PTHrP 1-34 primarily stimulated PKA signaling, and PTH 1-34 equally stimulated PKA and PKC signaling.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009599	Nitroprusside	A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.	Nitroferricyanide,Sodium Nitroprusside,Cyanonitrosylferrate,Ketostix,Naniprus,Nipride,Nipruton,Nitriate,Nitropress,Nitroprussiat Fides,Nitroprusside, Disodium Salt,Nitroprusside, Disodium Salt, Dihydrate,Disodium Salt Nitroprusside,Nitroprusside, Sodium
D010281	Parathyroid Hormone	A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.	Natpara,PTH (1-84),PTH(1-34),Parathormone,Parathyrin,Parathyroid Hormone (1-34),Parathyroid Hormone (1-84),Parathyroid Hormone Peptide (1-34),Hormone, Parathyroid
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D005269	Femur	The longest and largest bone of the skeleton, it is situated between the hip and the knee.	Trochanter,Greater Trochanter,Lesser Trochanter,Femurs,Greater Trochanters,Lesser Trochanters,Trochanter, Greater,Trochanter, Lesser,Trochanters,Trochanters, Greater,Trochanters, Lesser
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001158	Arteries	The vessels carrying blood away from the heart.	Artery
D014664	Vasodilation	The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.	Vasodilatation,Vasorelaxation,Vascular Endothelium-Dependent Relaxation,Endothelium-Dependent Relaxation, Vascular,Relaxation, Vascular Endothelium-Dependent,Vascular Endothelium Dependent Relaxation