Patterning of renal cGMP production by the natriuretic peptide receptor type A and blood pressure in spontaneously hypertensive rats.
Although important advances have been made over past decades in studying the mechanisms of hypertension, the nature of cellular signaling patterns involved and their relationship remain unclear. High cGMP production rates in isolated renal glomeruli have been presented as a characteristic of spontaneously hypertensive rat (SHR) even before the development of hypertension, which suggests that this event might be a cause of the increase in blood pressure. Using cross-breeding between SHR and WKY parental strains to obtain F1 and F2 hybrids, we have investigated the patterning of high blood pressure and cGMP production rates. We have found that, in the F2 population, the mean blood pressure and both basal and ANP(1-28)-stimulated cGMP production are similar to the parental SHR. In addition, we have found a positive correlation between blood pressure and high cGMP production rates in the F2 population. The higher cGMP production was not a consequence of hypertension, since in DOCA-salt hypertensive rats cGMP production was similar to that observed in normotensive WKY rats. These observations suggest that high cGMP production is a characteristic linked to hypertension. Finally, reciprocal crosses between the SHR and WKY parental strains showed that in the F1 population blood pressure but not cGMP production are associated with the Y chromosome.
Woodard
Geoffrey E
GE
Physiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK. GeoffreyW@intra.niddk.nih.gov
Zhao
Jing
J
Rosado
Juan A
JA
Brown
John
J
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000096:biosynthesis*; D006973:Hypertension; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017461:Receptors, Atrial Natriuretic Factor / Q000096:biosynthesis*; D013599:Systole; D014998:Y Chromosome
D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP