Parathyroid hormone-related peptide as a locally produced vasorelaxant: regulation of its mRNA by hypertension in rats.
The present study was undertaken to examine the effect of parathyroid hormone-related peptide (PTHrP) on the vascular tone as well as the expression of its mRNA in the cardiovascular system and its regulation in response to systemic hypertension in Sprague-Dawley rats. In aortic rings precontracted with 0.3 microM norepinephrine PTHrP(1-34) caused a dose-dependent relaxation with the maximal response of 33% being observed at 10(-6) M. PTHrP was nearly equipotent to PTH or CGRP in the vasodilatory action. Ribonuclease protection assay and Northern blot analysis demonstrated that PTHrP mRNA levels in the heart and aorta were increased as a result of systemic hypertension induced by constant infusion of angiotensin II and salt loading. The results of our in vivo studies suggest an autocrine/paracrine role for PTHrP as a local regulator of the vascular tone.
Takahashi
K
K
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Inoue
D
D
Ando
K
K
Matsumoto
T
T
Ikeda
K
K
Fujita
T
T
D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000096:biosynthesis* / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary; D019379:Teriparatide; D014158:Transcription, Genetic; D014664:Vasodilation / Q000187:drug effects
C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D012333:RNA, Messenger; D012982:Sodium, Dietary; D019379:Teriparatide; D000804:Angiotensin II; C054296:parathyroid hormone-related protein (1-34); D009638:Norepinephrine