In this study, we investigated the central as well as the regional hemodynamics of spontaneous hypertension in different phases using the reference sample microsphere method in conscious, unrestrained spontaneously hypertensive rats (SHR) using age-matched progenitor Wistar Kyoto rats (WKy) as controls. Moreover, in order to study the role of intravascular fluid volumes and their regional distribution in the early hemodynamics of spontaneous hypertension, we measured albumin distribution spaces at different ages in SHR and WKy. Microsphere studies showed an increase of cardiac output in 5 weeks old SHR when compared to age-matched WKy. This increased flow was mainly transmitted to the muscular and skin vascular bed. The kidney vascular resistance was increased significantly already in 5 weeks old SHR. In 7-8 weeks old animals, cardiac output was not significantly different in SHR and WKy. The increase in blood pressure was then characterized by a generalized increase in vascular resistance in almost all tissues. Plasma volume (PV) measurements indicate a significantly higher PV in 5 weeks old SHR when compared to age-matched WKy. At later ages (7-16 weeks), PV was lower in SHR than in WKy. Regional measurements show a consistently lower PV in gut, muscle, testes, and skin in SHR. It is concluded that the early increase in cardiac output in SHR is related to an increased central intravascular volume, possibly because of renal fluid retention. Moreover, the later further rise in blood pressure and increase in total peripheral resistance seem to be caused by an independent secondary rise in vascular resistance of all vascular beds.

No abstract

A method is described for providing chronic access to the right renal artery of unrestrained rats. It consists of insertion of a very thin (OD 0.2 mm) catheter into the right suprarenal artery of Wistar rats. The suprarenal artery originates from the right renal artery. After the cannula has been guided subcutaneously to the neck, it is connected to an Alzet osmotic minipump. The method has a success ratio of over 90% for periods up to 14 days. In the present study, we investigated the effects of catheter implantation on renal hemodynamics in uninephrectomized rats that were infused with saline for 2, 6, or 14 days. Values were compared with those obtained in control rats. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated from plasma clearances of 51Crethylenediaminetetraacetic acid and 125I-p-aminohippuric acid, respectively. Mean arterial pressure was between 107 +/- 2 and 116 +/- 2 mmHg in all animals. Neither GFR nor ERPF was influenced by catheter implantation. It is concluded that the method does not interfere with renal function.

1 The cardiovascular e ects by g 2 -melanocyte-stimulating hormone (g 2 -MSH) are probably not due to any of the well-known melanocortin subtype receptors. We hypothesize that the receptor for PheMet-Arg-Phe-amide (FMRFa) or Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-amide (neuropeptide FF; NPFFa), other Arg-Phe containing peptides, is the candidate receptor. Therefore, we studied various Arg-Phe containing peptides to compare their haemodynamic pro®le with that of g 2 -MSH(6 ± 12), the most potent fragment of g 2 -MSH. 2 Mean arterial pressure (MAP) and heart rate (HR) changes were measured in conscious rats after intravenous administration of g 2 -MSH related peptides. 3 Phe-Arg-Trp-Asp-Arg-Phe-Gly (g 2 -MSH(6 ± 12)), FMRFa, NPFFa, Met-enkephalin-Arg-Pheamide (MERFa), Arg-Phe-amide (RFa), acetyl-Phe-norLeu-Arg-Phe-amide (acFnLRFa) and desamino-Tyr-Phe-norLeu-Arg-Phe-amide (daYFnLRFa) caused a dose-dependent increase in MAP and HR. g 2 -MSH(6 ± 12) showed the most potent cardiovascular e ects (ED 50 =12 nmol kg 71 for DMAP; 7 nmol kg 71 for DHR), as compared to the other Arg-Phe containing peptides (ED 50 =177 ± 292 nmol kg 71 for DMAP; 130 ± 260 nmol kg 71 for DHR). 4 Peptides, which lack the C-terminal Arg-Phe sequence (Lys-Tyr-Val-Met-Gly-His-Phe-Arg-TrpAsp-Arg-Pro-Gly (g 2 -pro 11 -MSH), desamino-Tyr-Phe-norLeu-Arg-[L-1,2,3,4 tetrahydroisoquinoline-3-carboxylic acid]-amide (daYFnLR[TIC]a) and Met-enkephalin (ME)), were devoid of cardiovascular actions. 5 The results indicate that the baroreceptor re¯ex-mediated reduction of tonic sympathetic activity due to pressor e ects is inhibited by g 2 -MSH(6 ± 12) and that its cardiovascular e ects are dependent on the presence of a C-terminal Arg-Phe sequence. 6 It is suggested that the FMRFa/NPFFa receptor is the likely candidate receptor, involved in these cardiovascular e ects.