Increased expression of parathyroid hormone-related peptide gene in blood vessels of spontaneously hypertensive rats.
We have shown recently that mechanical stretch of cultured rat aortic smooth muscle cells induces a marked increase in gene expression of the vasorelaxant parathyroid hormone-related peptide. In the present study, we investigated whether mechanical force affected the in vivo parathyroid hormone-related peptide gene expression in blood vessels. Northern blot analysis revealed that stretch of isolated rat aortic strips increased the expression level of parathyroid hormone-related peptide mRNA. The parathyroid hormone-related peptide transcript level in aorta and mesenteric vessels from 18-week-old spontaneously hypertensive rats (SHR) was 2.5- and 2.2-fold higher, respectively, compared with age-matched Wistar-Kyoto (WKY) controls, whereas the parathyroid hormone-related peptide mRNA level in aorta from normotensive 4-week-old SHR was similar to that of age-matched WKY controls. The aortic parathyroid hormone-related peptide content was higher in 18-week-old SHR than in age-matched WKY controls. Moreover, treatment of mature SHR with an angiotensin II type 1 receptor antagonist or hydralazine caused a concomitant decrease in the parathyroid hormone-related peptide transcript level in aorta with lowering of blood pressure. These results suggest that the in vivo parathyroid hormone-related peptide gene expression in blood vessels is under the control of mechanical force, pointing to a role of parathyroid hormone-related peptide in the regulation of vascular tone.
Noda
M
M
Department of Cardiovascular Biology, Faculty of Medicine, University of Tokyo, Japan.
Katoh
T
T
Kurokawa
K
K
Takuwa
Y
Y
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001011:Aorta / Q000378:metabolism / Q000502:physiology; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology; D001808:Blood Vessels / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006830:Hydralazine / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D066298:In Vitro Techniques; D008297:Male; D044162:Parathyroid Hormone-Related Protein; D010812:Physical Stimulation; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000502:physiology; D013777:Tetrazoles
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger; D013777:Tetrazoles; D006830:Hydralazine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; C077793:candesartan cilexetil