title: Altered balance of main vasopressor and vasodepressor systems in rats with genetic hypertension and hypertriglyceridaemia.
abstract: The precise role of nitric oxide (NO) in hypertension is still not fully understood, although this vasodilator system represents the main counterbalance of major pressor systems. The aim of our study was to determine the contributions of superoxide anions, the renin-angiotensin system (RAS), the sympathetic nervous system (SNS) and NO to the maintenance of blood pressure (BP) in Prague hereditary hypertriglyceridaemic (HTG) rats with genetic hypertension. Conscious chronically cannulated rats were subjected to the consecutive blockade of the RAS (losartan, 10 mg/kg), the SNS (pentolinium, 5 mg/kg) and NO synthase [N(omega)-nitro-L-arginine (L-NAME), 30 mg/kg]. Some additional rats were pretreated with tempol (a membrane-permeable mimetic of superoxide dismutase). A subsequent genetic study in HTG x Lewis F(2) hybrid rats (n=284) was designed to reveal potential associations of particular BP components with baseline BP. The progenitor study indicated that BP elevation was more pronounced in male than female HTG rats (as compared with normotensive Lewis controls). Higher BP in HTG rats was due to the increased residual BP (measured after combined RAS and SNS blockade) and the augmentation of BP responses to tempol or losartan. In contrast, BP responses to pentolinium or l-NAME were similar in all experimental groups. It should, however, be noted that the baseline BP of progenitor animals was correlated positively with both residual BP and the magnitude of the BP response to pentolinium, but not with BP response to L-NAME. Similarly, the baseline BP of F(2) hybrid rats was positively associated with residual BP, the BP response to pentolinium and the relative SNS contribution to BP maintenance [expressed as a percentage of baseline mean arterial pressure (MAP) values], as well as with the ratio of BP changes elicited by ganglion blockade and NO synthase inhibition (Delta MAP(pentolinium)/Delta MAP(L-NAME) ratio), reflecting the balance of main vasopressor and vasodepressor systems. Thus our studies, performed in progenitor and F(2) hybrid rats, revealed that changes in BP induced by L-NAME do not keep pace with the progressive augmentation of pentolinium-induced changes in BP occurring over a wide range of increasing BP. The altered balance between enhanced SNS-dependent vasoconstriction and unchanged NO-dependent vasodilation ('relative NO deficiency' in rats with high BP) might result in BP elevation in this form of genetic hypertension.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, and Center for Experimental Research of Cardiovascular Diseases, CZ-142 20 Prague, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kunes
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Dobesová
authors.forename: Josef
authors.initials: J
authors.lastname: Zicha
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000235:genetics* / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010425:Pentolinium Tartrate / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D012737:Sex Factors; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects
chemical_list: D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D013113:Spin Labels; D013481:Superoxides; D009569:Nitric Oxide; D010425:Pentolinium Tartrate; D019001:Nitric Oxide Synthase; D019808:Losartan; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester